| <\/td>\n | Source (name of organization, etc.)<\/td>\n | Recommended weight gain1<\/sup><\/td>\n| Objective<\/td>\n<\/tr>\n | \n<\/tead><\/p>\n A<\/th>\n | U.S. Institute of Medicine (IOM) (2009)<\/td>\n | BMI <18.5 (underweight): 12.7–18.1 kg | BMI 18.5–25 (normal): 11.3–15.9 kg BMI 25–30 (overweight)2<\/sup>: 6.8–11.3 kg BMI \u226530 (obese): 5.0–9.1 kg<\/td>\n Appropriate birth weight3<\/sup><\/td>\n<\/tr>\n | B<\/th>\n | The Committee on Perinatology, Japan Society of Obstetrics and Gynecology (FY2021)<\/td>\n | BMI <18.5 (underweight): 12–15 kg | BMI 18.5–less than 25 (normal weight): 10–13 kg BMI 25–less than 30 (class 1 obesity): 7–10 kg BMI \u226530 (class 2 obesity): Tailored to the individual (generally up to a maximum of 5 kg)<\/td>\n Minimize the risk of pregnancy complications<\/td>\n<\/tr>\n | C<\/th>\n | MHLW4<\/sup> | Dietary Guidelines for Pregnant and Lactating Women Starting Before Pregnancy<\/td>\n BMI <18.5 (underweight): 12–15 kg | BMI 18.5–less than 25 (normal weight): 10–13 kg BMI 25–less than 30 (class 1 obesity): 7–10 kg BMI \u226530 (class 2 obesity and above): Tailored to the individual (generally up to a maximum of 5 kg)<\/td>\n Minimize the risk of pregnancy complications<\/td>\n<\/tr>\n | D<\/th>\n | Retrospective cohort study of 419,000 pregnant women in Japan<\/td>\n | BMI <18.5 (underweight): 13.0–13.9 kg | BMI 18.5–less than 25 (normal weight): 11.0–11.9 kg BMI 25–less than 30 (class 1 obesity): 8.0–8.9 kg BMI \u226530 (class 2 obesity): Risk reduction plateaus at 5 kg<\/td>\n Minimize the risk of pregnancy complications<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n | \n 1 <\/div>\n Uses a BMI (kg\/m2) calculated based on self-reported pre-pregnancy weight.<\/div>\n<\/div>\n \n 2 <\/div>\n A BMI of 25–30 kg\/m2 is considered overweight in the U.S. (classed as preobese in WHO standards), while a BMI of 30 kg\/m2 or above is considered obese.<\/div>\n<\/div>\n \n 3 <\/div>\n Sets a target of a birth weight of 3,000–4,000 g in the 39th–40th week of pregnancy.<\/div>\n<\/div>\n \n 4 <\/div>\n Since FY2021, the Children and Families Agency has overseen public awareness and related initiatives.<\/div>\n<\/div>\n Source: Dietary Reference Intakes for Japanese (2025 edition, MHLW)<\/small><\/p>\n Many studies have reported associations of maternal pre-pregnancy BMI and gestational weight gain with pregnancy complications and infant birth weight. A number of guidelines have been formulated based on these findings.<\/p>\n<\/div>\n<\/div>\n Professor Kato cites the Developmental Origins of Health and Disease (DOHaD) hypothesis as a key concept for understanding the importance of preventing underweight in pregnancy.<\/p>\n “Emerging in the 1980s, the DOHaD hypothesis is based on the idea that the environment during the fetal stage and in infancy determines the subsequent risk of lifestyle diseases,” he explains.<\/p>\n Scientists have conventionally regarded lifestyle diseases as being caused by diet and lifestyle in adulthood. However, in the 1980s, British epidemiologist Dr. David Barker discovered that people who weighed less at birth (low birth weight infants) had a higher risk of dying of coronary artery disease, high blood pressure, and diabetes as adults. He argued that birth weight, a reflection of the intrauterine environment, influences health throughout life.<\/p>\n “The case study best known for providing compelling support for this hypothesis is that of the Dutch Hunger Winter, which occurred toward the end of World War II.”<\/p>\n A dramatically increased risk of developing lifestyle diseases<\/h2>\nFrom the winter of 1944 until the beginning of 1945, during the final phase of World War II, the German army imposed a harsh blockade on food and fuel shipments to Amsterdam and other Dutch cities. Residents of those areas suffered such severe food shortages that they sought to stave off hunger by eating tulip bulbs, and around 20,000 people are said to have died of starvation.<\/p>\n “In the 2000s, the results of decades-long studies of children born to women who were pregnant at that time began to be published,” Kato continues. “From these, we discovered that children born to mothers who had been through pregnancy during this stringent blockade had a dramatically increased risk of developing diabetes, hypertension, and other lifestyle diseases as adults.”<\/p>\n Why do children born under conditions of nutritional deprivation later develop disease? Professor Kato explains the mechanism using the term “thrifty programming” (Figure 1).<\/p>\n ![\"\"](\"https:\/\/healthist.net\/en\/wp-content\/uploads\/sites\/3\/2026\/07\/297_en_feature01_04_fig01.png\") <\/small><\/p>\nFigure 1. <\/span>Mechanism of thrifty programming<\/span><\/strong>The mother rat\u2019s low-protein diet causes fetal undernutrition, producing offspring with high salt sensitivity and increased susceptibility to hypertension and stroke.<\/p>\n<\/div>\n “Organisms are equipped with survival strategies to enable them to withstand harsh environments. When the mother’s body lacks adequate nutrition, the fetus predicts that food will continue to be scarce once it is born, so the infant is born with thrifty programming that will enable it to live even on small amounts of energy.”<\/p>\n The fetus creates its body from a fertilized egg in accordance with its genetic information. And that is not all. The fetus receives environmental information from the mother’s body and adjusts its development in response. This means that if the mother is starving, the fetus will develop a body that readily stores energy and has a thrifty metabolism, because it interprets its environment as one in which food is scarce.<\/p>\n “When children with thrifty programming are raised on an unexpectedly abundant diet after their birth, a mismatch occurs between their thrifty programming and their actual environment,” Kato says. “More specifically, it gives rise to catch-up growth.” <\/p>\n If babies that were undernourished in the womb are fed abundant nutrients after being born, their bodies increase in weight and height at a rapid pace, in an effort to make up for their delayed growth. In other words, catch-up growth is a phenomenon whereby individuals whose growth had been temporarily delayed by undernutrition or illness, for example, demonstrate faster-than-normal growth after their nutritional status improves, in an effort to catch up to their original growth curve.<\/p>\n This is a natural reaction that makes up for growth delays, and such individuals appear at first glance to be growing normally. However, this rapid catch-up can adversely affect future health.<\/p>\n “That’s because, when there’s a sudden, large influx of nutrients into a body in the energy-conservation mode established by thrifty programming, the internal organs and metabolic functions can’t keep up, making the body more prone to insulin resistance and related metabolic abnormalities.”<\/p>\n Among the different kinds of nutrients, intake levels of protein—the source of nutrition for building organs and other parts of the body—in particular are known to have a powerful influence in relation to DOHaD. In experiments on rats, Professor Kato investigated the effects of restricting protein during pregnancy.<\/p>\n “In experiments using stroke-prone spontaneously hypertensive rats (SHRSP), pregnant rats were given either feed whose protein content had been halved or normal feed, and their offspring were raised to adulthood. Once those offspring had reached adulthood, we administered saline solution to all of them and compared their blood pressure changes and survival rates.” (Figure 2)<\/p>\n Figure 2. <\/span>Blood pressure and survival following salt loading<\/span><\/strong>In experiments using SHRSP, the offspring and grand-offspring of dams fed either a low-protein diet or a normal diet were given saline to drink from 10 weeks of age. Both the offspring and grand-offspring of dams that were undernourished during pregnancy showed greater susceptibility to hypertension and died earlier.<\/p>\n<\/div>\n A very clear difference emerged in the results of the experiments.<\/p>\n The offspring in the group whose mothers were undernourished during pregnancy developed a markedly greater increase in blood pressure in response to the saline solution compared with the rats in the group whose mothers had received normal feed.<\/p>\n In addition, those in the undernourished group suffered strokes earlier than the young rats in the group whose mothers had been well nourished during pregnancy and died in rapid succession.<\/p>\n Professor Kato and his team also discovered that even where the offspring ate normal feed during their own pregnancies, if the “grandmother” rats had been undernourished during pregnancy, the grandchildren also developed higher blood pressure and died earlier.<\/p>\n “In other words,” he says, “where rats are undernourished in the womb, their vulnerability to salt (salt sensitivity) is passed on to their own grandchildren’s generation.”<\/p>\n Why does this occur?<\/p>\n “When we investigated, we found that the kidneys and adrenal glands of the offspring of SHRSP rats fed a low-protein diet during pregnancy showed reduced expression of angiotensin receptor type 2 (AT2<\/sub>R), whose role includes lowering blood pressure and protecting blood vessels.”<\/p>\n Protein deficiency during fetal development in the womb would appear to be one cause of the decreased ability to properly control blood pressure even after birth.<\/p>\n This gives rise to the same question. Why does this occur?<\/p>\n “It appears to be diet-induced epigenetic changes,” Kato says.<\/p>\n This refers to the acquired mechanism whereby diet controls the switches for gene expression (function) without altering the DNA base sequence (genetic information) in our bodies.<\/p>\n “Our genes themselves don’t change,” he explains. “However, the foods and nutrients we consume, and habits such as when we eat, can turn our gene expression switches on or off.”<\/p>\n He says research has confirmed that exposure to a low-protein environment at the fetal stage causes chemical changes called DNA methylation (a switch that regulates gene function) in the At2r gene in the kidneys, resulting in altered gene function (changes in mRNA expression).<\/p>\n Professor Kato also explained a different example.<\/p>\n “Undernutrition in the womb alters the DNA methylation state of a gene called Ptger1<\/i> in the kidneys. This change in methylation causes Ptger1<\/i> to become overactive. When salt is consumed later in life, the effects of the overactive Ptger1<\/i> impair sodium regulation, making the rats more prone to hypertension as a result.”<\/p>\n High blood pressure has long been attributed to lifestyle and genes, but the results of these studies present the new perspective that the fetal environment is a factor contributing to individual differences in hypertension.<\/p>\n Based on the discussion so far, Professor Kato points out that there are two issues in need of improvement when it comes to nutritional guidance for pregnant women.<\/p>\n The first is the setting of more appropriate target values for nutritional intake during pregnancy. For example, protein consumption during pregnancy is essential for maternal blood production and for fetal cell division and development. Accordingly, the MHLW’s Dietary Reference Intakes for Japanese (2020) recommends that women in the second trimester of pregnancy add an extra 5 g to the recommended intake of 50 g\/day for women aged 18 and older, rising to an extra 25 g during the third trimester of pregnancy.<\/p>\n “There are two ways to measure protein: the nitrogen balance method (based on the quantity of nitrogen ingested and excreted) and the indicator amino acid oxidation method (based on the amino acid metabolic rate),” he explains. “Some have pointed out that the former underestimates the protein requirement to a quite substantial degree. As the figures set out by the MHLW are based on the nitrogen balance method, this suggests that the conventional protein requirement may be considerably lower than it should be.”<\/p>\n In addition, a great deal of attention is now focusing on folate—a vitamin that is particularly crucial to normal fetal development—from a DOHaD perspective. However, in Japan, the fact that both the reference value and the actual level of intake are low is a problem.<\/p>\n “I believe we should take steps to remedy the situation by reflecting the outcomes of DOHaD research in setting appropriate intake levels.”<\/p>\n The second issue is ensuring that uniform nutritional guidance evolves into something more individualized. That is to say, the vision for the nutritional science of the future depicted by Professor Kato is precision guidance based on each individual’s data.<\/p>\n “For example,” he continues, “nutritional guidance today is uniform, with everything lumped together in the categories of the second trimester or third trimester of pregnancy. However, we’d ideally provide optimal nutrition tailored to the individual by taking into account both their genotype and their current physical condition. We call this precision nutrition.”<\/p>\n In recent years, services that analyze people’s individual genetic information have become increasingly accessible. These provide an understanding of an individual’s genetic makeup, ranging from everyday things like whether one has a high or low tolerance to alcohol, for example, to a person’s blood iron levels or allergy risk.<\/p>\n “While the information in our genome remains unchanged throughout our lives, our epigenetics, gut flora, and data on such parameters as sleep and exercise change constantly. It would be great if we could achieve widespread availability of nutritional guidance based on monitoring these indicators in real time, using AI and the like to analyze them, and identifying the optimum diet for each individual at that particular moment.”<\/p>\n However, the major barrier confronting us in this regard is cost. This is because providing personalized dietary guidance and meals based on this in hospitals and other contexts requires considerable expenditure on personnel, as well as effort.<\/p>\n “We might find that implementation begins with meals for patients, or for athletes and others in fields requiring high performance levels,” Kato suggests.<\/p>\n Nevertheless, he is hopeful about the prospects for implementing and popularizing this next generation of nutritional guidance. At the same time, however, it is a fact that when information on television shows or the internet suggests a food is good for our health, that food disappears from stores the very next day. Professor Kato cautions against this kind of simplistic food faddism.<\/p>\n “When people hear that something is good for them, they tend to consume it to excess. What’s important is to lay the foundations by eating a well-balanced diet, and then adding things that are good for us on top of that.”<\/p>\n So, what can we do to achieve this?<\/p>\n “It’s vital to inform people of the evidence through education,” Kato says. “What’s also important is to understand the nature of one’s own genes, and to learn about one’s current state. That’s because doing so can help prevent diseases and enable us to take steps to lead a healthy life. And that won’t only benefit ourselves; it’ll also benefit our children and grandchildren.”<\/p>\n Such next-generation nutritional guidance, based on epigenetics and precision nutrition, would enable registered dietitians to provide personalized nutritional guidance tailored to each individual’s background and grounded in scientific evidence. While cost and technological challenges remain, this is a highly desirable direction for the future.<\/p>\n It has long been conventional wisdom that women must not put on too much weight in pregnancy. Today, however, undernutrition and underweight during pregnancy in particular are posing a problem, because nutritional status in the womb could potentially have a major impact on the child’s future risk of developing lifestyle diseases. There are even reports that lack of protein at the fetal stage could place the child at risk of impaired blood pressure regulation later in life. Scientists believe that this is because the mother’s diet during pregnancy affects epigenetics, which controls gene function. It has also become apparent that the mother’s nutritional status can even affect her grandchildren.<\/p>\n","protected":false},"author":2,"featured_media":2704,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[15],"tags":[],"class_list":["post-2694","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-nutrition"],"acf":{"author":"text by Toshiko Mogi","intro":" It has long been conventional wisdom that women must not put on too much weight in pregnancy. Today, however, undernutrition and underweight during pregnancy in particular are posing a problem, because nutritional status in the womb could potentially have a major impact on the child’s future risk of developing lifestyle diseases. There are even reports that lack of protein at the fetal stage could place the child at risk of impaired blood pressure regulation later in life. Scientists believe that this is because the mother’s diet during pregnancy affects epigenetics, which controls gene function. It has also become apparent that the mother’s nutritional status can even affect her grandchildren.<\/p>","person":[{"acf_fc_layout":"personcontent","personimg":2690,"personsholder":"Professor, Japan Nutrition University","personname":"Hisanori Kato","persondetail":"Graduated from the Department of Agricultural Chemistry at the University of Tokyo’s Faculty of Agriculture. He went on to obtain a Ph.D. in agriculture from the same institution in 1990. From 1991, he was a guest researcher at the U.S. National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases Diabetes Branch. In 1993, he became an assistant professor at Utsunomiya University’s School of Agriculture, and was subsequently appointed an assistant professor at the University of Tokyo’s Graduate School of Agricultural and Life Sciences in 1999. In 2009, he took up the post of project professor at the University of Tokyo’s Organization for Interdisciplinary Research Projects before becoming a project professor at the same university’s Graduate School of Agricultural and Life Sciences in 2017. He has held his current role since 2023. In 2024, he received the Japanese Society for Amino Acid Sciences Award for Distinguished Investigator. He has authored many books, for general and specialist readers alike."}],"issue":2673,"custom_css":".entry-content .v297_feature01_04_table01_wrapper{\r\noverflow-x:auto;\r\noverflow-y:hidden;\r\n}\r\n.entry-content .v297_feature01_04_table01{\r\nborder:#666 solid 1px;\r\nborder-collapse:collapse;\r\nwidth:100%;\r\n}\r\n.entry-content .v297_feature01_04_table01 thead tr td{\r\nbackground-color:#eeeeef;\r\nborder:#666 solid 1px;\r\nfont-size:13px;\r\nfont-weight:normal;\r\nline-height:1.2;\r\npadding:.2rem .1rem;\r\ntext-align:center;\r\nvertical-align:middle;\r\n}\r\n.entry-content .v297_feature01_04_table01 tbody tr th,\r\n.entry-content .v297_feature01_04_table01 tbody tr td{\r\nbackground-color:#fceef4;\r\nborder:#666 solid 1px;\r\nfont-size:14px;\r\nfont-weight:normal;\r\nline-height:1.2;\r\npadding:.2rem .1rem;\r\ntext-align:left;\r\nvertical-align:middle;\r\n}\r\n.entry-content .v297_feature01_04_table01 tbody tr th{\r\nfont-size:18px;\r\ntext-align:center;\r\n}\r\n.entry-content .v297_feature01_04_table01 tbody tr:nth-child(even) th,\r\n.entry-content .v297_feature01_04_table01 tbody tr:nth-child(even) td{\r\nbackground-color:#fffde4;\r\n}\r\n.entry-content .v297_feature01_04_table01 tbody tr td:nth-of-type(2){\r\nwidth:28%;\r\n}\r\n.entry-content .v297_feature01_04_table01 tbody tr td:nth-of-type(3){\r\nwidth:50%;\r\n}\r\n.entry-content .v297_feature01_04_table01 sup{\r\ncolor:#990000;\r\nfont-size:xx-small;\r\nfont-weight:500;\r\n}\r\n.entry-content .v297_feature01_04_caption_wrapper{\r\nalign-items:flex-start;\r\ndisplay:flex;\r\nfont-size:x-small;\r\nfont-weight:normal;\r\njustify-cotent:flex-start;\r\nline-height:1.3;\r\ntext-align:left;\r\n}\r\n.entry-content .v297_feature01_04_caption_wrapper>div:first-of-type{\r\ncolor:#990000;\r\n}\r\n.entry-content .caption_sup{\r\nfont-size:xx-small;\r\n}\r\n"},"_links":{"self":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2694","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/comments?post=2694"}],"version-history":[{"count":0,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2694\/revisions"}],"acf:post":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/issue\/2673"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media\/2704"}],"wp:attachment":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media?parent=2694"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/categories?post=2694"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/tags?post=2694"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":2692,"date":"2026-07-09T10:02:35","date_gmt":"2026-07-09T01:02:35","guid":{"rendered":"https:\/\/staging.healthist.net\/en\/?p=2692"},"modified":"2026-07-10T16:34:14","modified_gmt":"2026-07-10T07:34:14","slug":"what-we-have-learned-about-epigenetics-so-far-the-potential-for-acquired-characteristics-to-be-passed-on-to-the-next-generation","status":"publish","type":"post","link":"https:\/\/healthist.net\/en\/biology\/2692\/","title":{"rendered":"Special Feature 1 \u2013 What We Have Learned About Epigenetics So Far <\/small>The potential for acquired characteristics to be passed on to the next generation"},"content":{"rendered":" Genes are regulated as to whether their functions are expressed by a mechanism called epigenetics, without any alteration to their underlying base sequences. Because of this epigenetic mechanism, even cells with the same DNA sequence have different properties.<\/p>\n While epigenetic information is passed on to subsequent generations in some species, such as plants, scientists originally believed that it was not inherited by the next generation in mammals. The starting point for this established theory was probably the idea that a new individual could not be created unless cell characteristics were reset. Our bodies have as many as 37 trillion cells of various different types, such as skin cells, liver cells, and blood cells. However, all these cells can be traced back to a single fertilized egg from which they proliferated. In other words, when it comes to the actual base sequence of genes, all cells basically contain the same information. The reason why each cell type has a different role despite this is that the genes they use, and the timing and extent of those genes\u2019 use differ from one cell type to another. Epigenetics is the mechanism that controls gene use in this way, with each individual cell containing epigenetic information tailored to its particular role.<\/p>\n However, if these cell-specific characteristics were maintained, a new individual could not be generated through reproduction. Accordingly, based on the idea that there was a need to first restore each cell to its original \u201cfresh\u201d state, scientists long believed that epigenetic information basically could not be passed on to the next generation.<\/p>\n Investigation of primordial germ cells and embryos immediately after fertilization has confirmed that epigenetic modifications are actually erased (Figure 1).<\/p>\n Figure 1. <\/span>The epigenetic reprogramming mechanism in the germ cell lineage<\/span><\/strong>Whole-genome DNA methylation levels in the mouse life cycle. The blue line indicates a high level of genomic DNA methylation in somatic cells. This methylation is established in the early stage of embryonic development. On the other hand, epigenetic reprogramming occurs in germ cells (yellow line). Whole-genome DNA demethylation occurs during primordial germ cell formation, followed by remethylation during the formation of eggs and sperm, and then further demethylation after fertilization.<\/p>\n<\/div>\n What has also provided support for this idea is genomic imprinting. Most genes are controlled in such a way that the alleles<\/span> derived from both father and mother are both expressed or suppressed. In imprinted genes, however, one is inactivated by means of DNA methylation, so that only the other one functions. We know that these epigenetic modifications are erased in primordial germ cells, and that they are reset anew in the gonads according to the sex of the individual. The existence of this reset mechanism has been regarded as evidence demonstrating that epigenetic states are not inherited across generations, as a general rule.<\/p>\n In other words, the view that the epigenetic state of the previous generation is reset when a new individual is born has for many years been accepted scientific knowledge, both theoretically and as an observed fact.<\/p>\n At the same time, there have been previous reports of cases suggesting that parental epigenetic information might actually be inherited by offspring. In a case published in 2012, involving a woman who had developed colon cancer, two of her five children also developed colon cancer and were found to have the same DNA methylation pattern in the same genes as their mother (Figure 2). This has given rise to the question of whether epigenetic information might, in some exceptional cases, remain without being erased.<\/p>\n Figure 2. <\/span>Example of colon cancer in which similar epigenetic changes were observed in a parent and their children<\/span><\/strong>Although the MLH1 gene is not normally methylated, abnormal methylation occasionally occurs and dramatically increases the risk of colon cancer. A woman who had developed multiple colon tumors and adenomas showed abnormal DNA methylation in this region. Two of her children also developed colon cancer and had epigenetic alterations in regions similar to those seen in their mother.<\/p>\n<\/div>\n Epigenetic modifications are added and removed according to the environment. This is because they play a part in maintaining the body\u2019s homeostasis and adapting to environmental changes by triggering the expression of the necessary genes. If abnormal epigenetic modifications arising from lifestyle or the environment are passed on to the next generation, they could potentially affect that generation\u2019s health in the future.<\/p>\n Accordingly, I have undertaken research using mouse models in an effort to prove empirically whether such epigenetic modifications really are inherited across generations.<\/p>\n The problem was that I could not completely rule out the possibility that mutations that appeared at first glance to be epigenetic were actually secondary results of mutations in the DNA sequence itself. Although there had been reports that epigenetic information appeared to be inherited in mice in experiments, proving that epigenetic inheritance was occurring was technically difficult at that time, so they went no further than reporting the phenomenon itself. For example, if a mutation occurs in a particular gene\u2019s DNA sequence, it may have the effect of altering the epigenetic state of its surroundings. Studies up to that point had unfortunately not managed to prove that this was purely epigenetic inheritance independent of any mutation in the DNA sequence.<\/p>\n What made it possible to prove this was the DNA methylation editing technology that we developed in 2017 (Figure 3). This technology introduces DNA methylation into a specific location without altering the DNA sequence at all. It is effectively like installing a methylation switch that is pressed once to alter the state of the gene, with the switch itself then immediately being removed. This technology can be used for such purposes as investigating the causal relationship between epigenetic abnormalities and diseases. For example, abnormal methylation in a specific location is often seen in cancer and a number of other diseases. However, it was previously difficult to determine whether the methylation was the cause of the disease or its result. Using this editing technology, we are now able to investigate the cause of diseases by artificially introducing a specific abnormal methylation pattern into normal cells. If we identify that the methylation abnormality is the cause, it might potentially lead to the development of a therapy targeting that area.<\/p>\n Figure 3. <\/span>DNA methylation editing technology<\/span><\/strong>CpG islands are mostly promoter regions of genes where CpG sequences\u2014sequences where cytosine (C) is followed by guanine (G)\u2014are concentrated. They are not normally methylated. DNA methylation editing is a technology for introducing DNA without CpGs (CpG-free DNA) into CpG islands to methylate them. After methylation, the CpG island remains methylated, even after removal of the introduced CpG-free DNA.<\/p>\n<\/div>\n Using this technology, we undertook an experiment in which we sought to distinguish between genetic and epigenetic inheritance. This enabled us to verify whether epigenetic information really is passed on across generations.<\/p>\n In the experiment, we created a mouse model that had been subject only to manipulation of its epigenetic information, without alteration of its DNA sequence, and then ascertained whether that information was maintained and affected the phenotype. Whereas the target gene in the parent mice was virtually 100% methylated, our investigation of their offspring showed a methylation level of around 50% in individuals that had inherited that allele from their father. This means that the artificially introduced methylation was passed on to the offspring via germ cells. From this result, we discovered the possibility that epigenetic information might linger across generations, without being completely erased in the process of development (Figure 4).<\/p>\n Figure 4. <\/span>Verification of transgenerational epigenetic inheritance using DNA methylation-edited mice<\/span><\/strong>Using DNA methylation editing technology, the research team produced DNA methylation-edited mouse embryonic stem cells and then DNA methylation-edited mice. When they examined whether the DNA methylation and associated phenotype were passed on to the offspring, the researchers found that expression of LDLR mRNA and protein in the liver was repressed, consistent with the methylation status. In addition, cholesterol levels were elevated in the offspring. This suggests that DNA methylation and associated phenotypes can be inherited by the next generation.<\/p>\n<\/div>\n Although this experiment revealed the possibility that methylation might be passed on to the next generation, it also raised an even bigger question: how is this methylation inherited? As described above, cells have a mechanism called epigenetic reprogramming, in which epigenetic information is reset in two stages in the process of development, and methylation is meant to be erased as part of this.<\/p>\n Accordingly, during the developmental process of these experimental mice, we conducted an experiment to investigate in greater detail the state of methylation in primordial germ cells, where the first major demethylation occurs during development. As a result, we discovered that DNA methylation is temporarily erased.<\/p>\n However, some highly interesting things occurred after that. For example, no DNA methylation was observed in the sperm of the F1 generation. But when we examined the offspring born from that sperm, DNA methylation had reappeared in their somatic cells. Moreover, it was being maintained at a stable level. In other words, although the sperm and egg carried DNA in a demethylated state into the next generation, methylation in the genes occurred once again in somatic cells after fertilization. This made me think that, rather than DNA methylation itself being directly inherited, there might be some kind of residual epigenetic memory that re-introduced methylation into the genes. That is to say, this information is carried into the next generation and the same abnormal methylation occurs again as a result. The phenomenon could be likened to a gene having a tendency of its own: even if the methylation is removed, it somehow returns to the same state. The question of what this epigenetic memory might be is one of my current research topics.<\/p>\n In explanations of genetics and evolution, the ideas of Charles Darwin and Jean-Baptiste Lamarck have long been contrasted with each other. In Darwin\u2019s view, organisms have individual variations from the outset, with only those best adapted to the environment tending to survive. To take the example of giraffes, those born with long necks were able to eat leaves higher up on trees and thus survived more easily, so their genes were passed on. In contrast, Lamarck believed that organisms altered their bodies during their lifetimes through effort and experience, and that those changes were then passed on to their descendants. His view was that giraffes that made the effort to stretch their necks so that they could eat the leaves on tall trees developed longer necks as a result and that their offspring then inherited those longer necks.<\/p>\n Leaving aside whether Lamarck\u2019s ideas were correct, our experiments suggest that epigenetic changes can be inherited, meaning that characteristics acquired by parents might be transmitted to the next generation.<\/p>\n Just like gene mutations, some epigenetic abnormalities probably occur by chance, while others are altered by behavioral or environmental impacts. Nevertheless, experiments have now shown that the phenomenon whereby these abnormalities are passed on across generations can occur.<\/p>\n At this point, we do not yet know whether such transgenerational epigenetic alterations occur in humans as well\u2014for example, whether epigenetic information arising from unhealthy lifestyles really can be passed on to a person\u2019s offspring, and which aspects of the epigenetic state of germ cells such lifestyles affect. That is precisely why I believe it is vital for us to understand the mechanisms involved. If we understand the mechanisms, we might be able to determine what kind of epigenetic information is erased and what kind remains in the next generation. I believe that this will be the first step toward being able to explain the relationship between the environment and genetics in the true sense.<\/p>\n Scientists long believed that epigenetic modifications were not inherited by the next generation, but rather reset when a new individual was born, because modifications of this kind employ tools such as methylation to regulate gene function without affecting the DNA base sequence. However, research has shown methylation beginning again in the offspring\u2019s somatic cells after fertilization. More specifically, it would appear that, rather than DNA methylation itself being inherited directly, a mechanism for reactivating methylation was at work. We therefore cannot deny the possibility that characteristics acquired by the parent might be passed on to the next generation.<\/p>\n","protected":false},"author":2,"featured_media":2699,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[16],"tags":[],"class_list":["post-2692","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-biology"],"acf":{"author":"composition by Rie Iizuka Scientists long believed that epigenetic modifications were not inherited by the next generation, but rather reset when a new individual was born, because these modifications regulate gene function through mechanisms such as DNA methylation without altering the DNA base sequence. However, research has shown methylation beginning again in the offspring\u2019s somatic cells after fertilization. More specifically, it would appear that, rather than DNA methylation itself being inherited directly, a mechanism for reactivating methylation was at work. We therefore cannot deny the possibility that characteristics acquired by the parent might be passed on to the next generation.<\/p>","person":[{"acf_fc_layout":"personcontent","personimg":2686,"personsholder":"Associate Professor, International Research Center for Medical Sciences (IRCMS), Kumamoto University","personname":"Yuta Takahashi","persondetail":"In 2011, he successfully completed a doctoral program at the University of Tsukuba\u2019s Graduate School of Life and Environmental Sciences, receiving a Ph.D. in Biotechnology. While undertaking postdoctoral training at the Salk Institute for Biological Studies in the U.S., in the laboratory of Professor Juan Carlos Izpisua Belmonte between 2012 and 2022, he developed a DNA methylation editing technology and demonstrated transgenerational epigenetic inheritance in mice. He then joined Altos Labs, Inc. in 2022, and took up his current post in 2024. Heading up the Laboratory of Epigenetic Inheritance, he is dedicated to shedding light on the mechanism involved in the transgenerational inheritance of epigenetic information."}],"issue":2673,"custom_css":""},"_links":{"self":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2692","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/comments?post=2692"}],"version-history":[{"count":0,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2692\/revisions"}],"acf:post":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/issue\/2673"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media\/2699"}],"wp:attachment":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media?parent=2692"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/categories?post=2692"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/tags?post=2692"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":2676,"date":"2026-07-09T10:01:03","date_gmt":"2026-07-09T01:01:03","guid":{"rendered":"https:\/\/staging.healthist.net\/en\/?p=2676"},"modified":"2026-07-10T16:34:21","modified_gmt":"2026-07-10T07:34:21","slug":"what-we-have-learned-about-epigenetics-so-far-genetic-factors-do-not-tell-the-whole-story-about-aging","status":"publish","type":"post","link":"https:\/\/healthist.net\/en\/medicine\/2676\/","title":{"rendered":"Special Feature 1 \u2013 What We Have Learned About Epigenetics So Far <\/small>Genetics do not tell the whole story of aging"},"content":{"rendered":" I am sure that everyone knows from their own experience that the way aging progresses differs from one individual to another, with some people remaining youthful while others appear remarkably aged despite being the same age. Even among monozygotic twins, whose DNA is virtually identical, the speed at which aging progresses and their lifespans differ depending on their environment and lifestyle during development. In other words, not only the mere passage of time and congenital heredity, but also acquired factors such as environment and lifestyle have a major influence on aging. While the degree of impact differs from one research report to another, acquired factors—as opposed to congenital factors—are said to account for anywhere between 50% and 80% of aging.<\/p>\n What changes as a result of acquired factors is the epigenome. The epigenome uses such tools as DNA methylation, histone modification, and changes in chromatin structure to control gene function (switching genes on and off) without altering the DNA base sequence (genetic information). Although all the body’s cells have the same DNA base sequence, each tissue fulfills its own unique role, because its cells have specific gene expression patterns; for instance, brain cells possess brain-specific epigenetic information, while liver cells have liver-specific epigenetic information.<\/p>\n However, this kind of cell-specific epigenome changes as we age, due to acquired factors including DNA damage, diseases such as metabolic disorders and infections, lifestyle, social stress, and external environmental factors such as exposure to ultraviolet rays and chemical substances. To take an analogy, if DNA is the whole closet, then it is as though the contents of the closet that were once neatly organized have become disordered. In this situation, the tissue cannot retrieve the things it needs (genes). Accordingly, sirtuins and other longevity genes play the part of housekeepers, tidying up the closet. That is to say, they maintain tissue function by modifying the epigenome and enabling the necessary genes to be retrieved. However, as these housekeepers also become less active as we age, the closet remains untidy. Once this happens, tissue function gradually declines, not only resulting in such phenomena of aging as reduced muscle strength, cognitive function, and immunocompetence, as well as skin aging, but also leading to the onset of diseases (Figure 1).<\/p>\n Figure 1. <\/span>The epigenome and aging<\/span><\/strong>Our epigenome changes as a result of acquired factors as we age, while the activity of the sirtuin genes that repair the epigenome declines. This makes it impossible to use the information required to maintain tissue function, like being unable to retrieve the things needed from a messy closet, resulting in such phenomena of aging as reduced muscle strength, cognitive function, and immunocompetence, as well as skin aging.<\/p>\n<\/div>\n We also know that epigenetic alterations are stored in cells and organs over the long term and are passed on through cell division. In other words, having an irregular lifestyle, such as eating and drinking to excess when young, will affect one’s aging in the future.<\/p>\n In addition, aside from epigenetic alterations, aging is also caused by mutations in which the gene sequence itself changes. Using our closet analogy, this is akin to the vacuum cleaner being replaced by a broom, and cancer is a typical disease that result from such changes.<\/p>\n In aging research today, 12 hallmarks of aging have been set out, and epigenetic alterations are positioned as one of them (Table 1). Crucially, these hallmarks of aging do not function in isolation; rather, they influence each other, with epigenetic alterations serving as an important key to shedding light on the mechanisms of aging.<\/p>\n Rather than having a single cause, aging progresses through the accumulation of multiple changes at the cellular level, as shown by the hallmarks of aging. Epigenetic alterations are regarded as one of the important hallmarks, so research efforts focused on them are gaining momentum worldwide.<\/p>\n<\/div>\n Aging research aimed at controlling lifespan has progressed worldwide since 1935, when, in a world first, an experiment on rats showed that limiting calories had a life-extending effect. In particular, various studies using mice and primates have demonstrated the basic mechanism behind the effect of calorie restriction in curbing the progression of aging; specifically, we know that it is down to the activation principally of the sirtuin gene SIRT1 by nicotinamide adenine dinucleotide (NAD+<\/sup>). As SIRT1 is a protein that controls the epigenome, attention has begun to focus on the epigenome. It has even been suggested that existing compounds such as metformin, which is a drug known for its use in treating type 2 diabetes, and the immunosuppressant rapamycin, could affect the epigenome and have anti-aging and life expectancy-extending effects. With research aimed at making cell rejuvenation possible even in elderly people also progressing right now, we are about to enter an age in which aging is regarded as a disease, where we can not only stem its progression, but potentially treat it.<\/p>\n In fact, until 2010 or so, the mainstream view was that while aging could be delayed, it could not be reversed. But is aging truly irreversible? At what point does aging occur and how does it progress? These questions provided the starting point for my development of ICE mice, in partnership with a team led by Dr. David Sinclair of Harvard University in the U.S. (Figure 2).<\/p>\n Figure 2. <\/span>Development of ICE mice<\/span><\/strong>When epigenetic alterations are induced in young mice, aging accelerates without changes in the DNA sequence. Epigenome improvements were observed as a result of restructuring this mouse’s epigenome, demonstrating the possibility that aging may be reversible.<\/p>\n<\/div>\n ICE mice are an accelerated aging model developed by performing procedures that induce epigenetic alterations in young mice by artificially damaging part of their DNA over a three-week period. In the process of the DNA damage being repaired, this resulted in reduced tissue function affecting memory, muscles, vision, and bone density, among others, as well as white hair and other phenomena of aging, without altering the DNA sequence. Additionally, we observed epigenetic alterations including DNA methylation, histone modification, and changes in chromatin structure in these ICE mice subject to accelerated aging. In particular, in mouse muscles, muscle-specific epigenetic information declined, while epigenetic modifications and gene expression in regions associated with immunity and inflammation increased.<\/p>\n From results such as these, we proved that, as described above, acquired stress (DNA damage) is stored in cells and organs as the epigenome, and that aging occurs when cell- or organ-specific epigenetic information is lost. It also became apparent that the epigenome determines the speed and timing of aging. Interestingly, we did not observe the progression of aging in mice when we reduced the period of DNA damage to two weeks. From this, we surmised that there is a threshold at which stress causes epigenetic information to be lost, and that aging progresses suddenly once that threshold is exceeded.<\/p>\n Next, we conducted an experiment in which we used Yamanaka factors to restructure (reprogram) the epigenome in these ICE mice. Discovered by Professor Shinya Yamanaka, who was awarded the Nobel Prize in Physiology or Medicine, the Yamanaka factors are a set of four genes that can reprogram cells to become induced pluripotent stem cells (iPS cells) capable of differentiating into the cells of all kinds of tissues. In this experiment, we used the three factors Oct3\/4, Sox2, and Klf4, omitting c-Myc because of the elevated risk of neoplastic transformation (tumor formation) arising from its powerful cell proliferation ability. We observed improvements in methylated DNA and parts of the epigenome as a result of inducing these Yamanaka factors, demonstrating the possibility that we might be able to treat aging.<\/p>\n Members of Dr. Sinclair’s laboratory subsequently succeeded in achieving vision recovery by rejuvenating optic nerve cells in a glaucoma model based on the application of ICE mice and reprogramming technology, with a clinical study on glaucoma patients scheduled to begin in 2026. Glaucoma is a disease in which damage to the optic nerve causes vision impairment and visual field defects, whose incidence rate increases with age. Given that there is currently no fundamental treatment to restore the optic nerve, we hope that this clinical study will produce positive outcomes.<\/p>\n Aging research aims not only to extend lifespan, but also to promote healthy longevity. In fact, extending healthy life expectancy requires the accurate, appropriate incorporation of a variety of approaches, including nutrition, exercise, and compounds such as supplements and medications. Particular attention should be paid to the intake of compounds thought to have a major impact on the body. In the case of the activation of the sirtuin gene by NAD+<\/sup> described above, for example, a nicotinamide mononucleotide supplement that increases NAD+<\/sup> has been developed. However, while taking it in the morning is effective, taking it in the evening could potentially accelerate aging. This is because the quantity of NAD+<\/sup> falls at night as part of the body’s circadian rhythm (an organism’s body clock, which fluctuates over a 24-hour cycle), and disrupting this rhythm causes metabolic disorders.<\/p>\n It is also very important to ascertain the degree to which aging has actually progressed, rather than looking at a person’s chronological age. This does not necessarily mean the time when an individual actually feels aging occurring. Some abnormalities occur at the molecular level well before phenomena of aging manifest themselves in a person’s appearance or body. Biological aging clocks are indicators used to visualize otherwise invisible aging.<\/p>\n A typical example used in aging research is called the epigenetic clock; this method measures epigenetic changes, such as methylation in the blood, which increase with advancing age. We ourselves used the epigenetic clock in the aforementioned ICE mice research. Also developed have been aging clocks that combine a variety of biomarkers, including proteins, metabolites, hormones, and immune function, whose use is progressing not only in aging research, but also in the provision of testing services, primarily overseas.<\/p>\n Understanding a person’s aging clock will enable us to provide an approach tailored to not simply an individual, but that individual’s organs and cells, rather than a uniform intervention method along the lines of “Your actual age is 30, but the biological age of your brain and heart is 50, so you should do this amount of this kind of exercise and consume this many grams of protein per day, and this supplement would be effective.” Another thing regarded as crucial is life design that takes an individual’s narrative as the starting point. Although everyone ought to understand the importance of improving their lifestyle for the sake of their health, many of us find it hard to start taking the practical steps required. However, life goals such as wanting to start a business at the age of 40 or wishing to go traveling with one’s grandchild next year are more powerful motivators for altering behavior than numerical changes. In order to design a biological aging clock tailored to each individual’s life design and extend their healthy life expectancy, I started up ASAGI Labs as both an incorporated foundation conducting basic research and a company promoting the commercialization of that research.<\/p>\n ASAGI Labs aims to develop a high-precision method of measuring biological age, using AI to analyze epigenetic changes and other biomarkers, data such as blood pressure and heart rate obtained via digital devices, and clinical data. In addition, we are building a list of drugs with the potential to extend healthy life expectancy, focusing on existing therapeutic drugs whose effectiveness and safety have already been demonstrated, as part of our research and development of foods and pharmaceuticals aimed at extending healthy life expectancy. Among them is ambroxol, the main component in expectorant drugs, which has antioxidant, anti-inflammatory, and autophagy-promoting effects, and is known to affect epigenetic alterations.<\/p>\n We plan to conduct a clinical study to evaluate improvements in such areas as cognition, muscle strength, and immune function in healthy individuals aged 50 or over to whom ambroxol has been administered. This clinical trial is participating in XPRIZE Healthspan, a global competition aimed at suppressing or improving aging in people aged 50–80 by at least 10 years. We are also developing a drug that controls specific epigenetic alterations in order to improve sarcopenia (muscle loss) arising from the use of GLP-1 receptor agonist drugs to treat diabetes and obesity.<\/p>\n Aging research centered on epigenetics, together with the social implementation of its findings, is expected to continue advancing worldwide. While the U.S. is currently the global leader in research and business focused on the regulation of aging, I believe Japan has strengths in this area, precisely because it is the most aged society in the world. At ASAGI Labs, too, we are undertaking joint research with the municipal governments of Shizuoka City, Fujinomiya City, and Fujieda City, in an effort to create products and services that support healthy life expectancy and thus promote the health of local citizens.<\/p>\n In the animal kingdom, Greenland sharks (Somniosus microcephalus<\/i>) show no signs of aging even when close to 400 years old, and Galapagos tortoises (Chelonoidis niger<\/i>) remain active and retain reproductive capacity even after the age of 100. The fact that living creatures do not necessarily age with the passage of years is a matter of endless interest to me as a biologist. With research into the genomes and epigenomes of long-lived creatures also progressing, we might one day reach a time when humans, too, live to be 250 years old.<\/p>\n Research into aging is progressing, amid a focus on anti-aging. While genetic factors are known to be involved in aging, acquired factors such as environment and lifestyle also have a major influence, with some scientists attributing more than half of aging to them. The main acquired factor is the epigenome, which controls gene function through DNA methylation, among others. As epigenetic alterations play a key role in shedding light on the mechanisms of aging, efforts to investigate the inhibition of aging and treatments that regard aging as a disease look set to advance worldwide.<\/p>\n","protected":false},"author":2,"featured_media":2677,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[14],"tags":[],"class_list":["post-2676","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicine"],"acf":{"author":"composition by Yumi Ohuchi Research into aging is progressing, amid a focus on anti-aging. While genetic factors are known to be involved in aging, acquired factors such as environment and lifestyle also have a major influence, with some scientists attributing more than half of aging to them. The main acquired factor is the epigenome, which controls gene function through DNA methylation, among others. As epigenetic alterations play a key role in shedding light on the mechanisms of aging, efforts to investigate the inhibition of aging and treatments that regard aging as a disease look set to advance worldwide.<\/p>","person":[{"acf_fc_layout":"personcontent","personimg":2680,"personsholder":"Associate Professor, Division of Aging Biology\r\nResearch Institute for Science and Technology, Tokyo University of Science","personname":"Motoshi Hayano","persondetail":"Graduated from Kumamoto University’s Faculty of Science in 2005. In 2011, he gained a Ph.D. in life sciences from the Department of Medical Genome Sciences at the University of Tokyo’s Graduate School of Frontier Sciences. After fellowships at Harvard Medical School in the U.S., including a Human Frontier Science Program (HFSP) Long-Term Fellowship, he was appointed an assistant professor at Keio University School of Medicine in 2017. He has held his current post since April 2025. He has also been involved in startups including Tsubota Laboratory, Inc. and One Genomics Inc., and has served as Chair of ASAGI Labs Foundation and CEO of ASAGI Labs Inc. since 2024. His research focuses on aging biology and epigenetics."}],"issue":2673,"custom_css":""},"_links":{"self":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2676","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/comments?post=2676"}],"version-history":[{"count":0,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2676\/revisions"}],"acf:post":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/issue\/2673"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media\/2677"}],"wp:attachment":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media?parent=2676"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/categories?post=2676"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/tags?post=2676"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":2675,"date":"2026-07-09T10:00:27","date_gmt":"2026-07-09T01:00:27","guid":{"rendered":"https:\/\/staging.healthist.net\/en\/?p=2675"},"modified":"2026-07-10T16:34:49","modified_gmt":"2026-07-10T07:34:49","slug":"what-we-have-learned-about-epigenetics-so-far-the-two-mechanisms-controlling-gene-function","status":"publish","type":"post","link":"https:\/\/healthist.net\/en\/medicine\/2675\/","title":{"rendered":"Special Feature 1 \u2013 What We Have Learned About Epigenetics So Far <\/small>The two mechanisms controlling gene function"},"content":{"rendered":" The term epigenetics is derived from the word “epigenesis,” a neologism coined by combining the Greek prefix “epi,” meaning “after,” with the English word “genesis,” meaning “creation” or “development.” It refers to changes in gene function that occur independently of changes in the DNA sequence in the process of body development and cell differentiation, and are passed onto daughter cells following cell division. It is a mechanism that determines which genes will or will not be used in each cell, and maintains that information over a long term.<\/p>\n Our entire body originates from a single fertilized egg. Tissues and organs, such as liver and brain, are produced through repeated cell division starting from a fertilized egg, which differentiates into a variety of cells. Each differentiated cell has all the estimated 20,000 or so human genes, but the genes actually used vary according to the type of cell. If we look at each of the approximately 37 trillion cells constituting our body, we can see that only a proportion of the genes are actually functioning; for example, red blood cells, which are specialized in producing hemoglobin, the number of functioning genes is just 100–200 or so. It is epigenetics that enables the selective use of genes. In the case of mammals including humans, this pattern of gene usage is re-established from scratch (from the initial state in the fertilized egg) in each generation. However, there are reports suggesting that some changes in gene usage caused by environmental factors or those occurring by chance might potentially be carried over to the next generation; research on such epigenetic inheritance is ongoing.<\/p>\n To understand epigenetics, let us take the example of induced pluripotent stem cells (iPS cells). iPS cells are cells that have been reset to the initial state of cell differentiation (reprogrammed) by introducing a specific set of genes into a somatic cell such as a skin or blood cell. iPS cells can therefore differentiate into any kind of cell, just as cells do immediately after fertilization. In this reprogramming process, all the epigenetic patterns in the cell are reset, creating an initial state close to that of a fertilized egg capable of becoming any kind of cell.<\/p>\n For simplicity, we here classify the epigenetic mechanisms into two types. One is DNA methylation. DNA is composed of four bases: guanine (G), adenine (A), thymine (T), and cytosine (C). Methylation of DNA is the reaction that adds a methyl group (CH3<\/sub>) to C. To put it very succinctly, when the part of DNA that regulates gene activity is methylated, the gene is switched off, whereas a gene with a non-methylated regulatory region can be more readily switched on. DNA methylation is a simple, one-way mechanism for suppressing gene activity.<\/p>\n In contrast, histone modification is diverse and complex. Histones are proteins consisting of chains of amino acids, around which DNA is wrapped (Figure 1). Not only methylation, but also other types of histone modification exist, including acetylation, phosphorylation, and ubiquitination. The biological meaning varies according to which modification occurs on which amino acid and also in which combination, allowing gene switches to be adjusted across subtle gradations: “fully on,” “fully off,” “partially suppressed,” and “easily switched on.” These modifications also increase the precision of gene expression while working in harmony with or against each other.<\/p>\n Figure 1. <\/span>Epigenetic modifications of histones<\/span><\/strong>A diverse array of epigenetic modifications occur in histones, which are proteins associated with DNA in cell nuclei. DNA is wrapped around a histone octamer, an assembly consisting of two molecules each of the histones H2A, H2B, H3, and H4. The chemical modifications of histones are carried out by various enzymes.<\/p>\n<\/div>\n Epigenetic pattern changes during the fetal stage, starting immediately after fertilization, through cell differentiation and development, but also throughout our lives after birth, potentially influenced by several factors, including stress, environment, and nutrition. Usually, this refers to long-term control of gene expression, but brief changes in histone modification lasting for a few hours to a few days may also be caused by environmental changes or exposure to specific chemicals. For example, if DNA is damaged by ultraviolet rays, radiation, or the like, histones are marked by specific modifications indicating the location of damage to attract repair proteins. Once the repair is complete, the marker is removed and the histones return to their original unmodified state. The repair of day-to-day cell damage is also the work of epigenetics.<\/p>\n The reactions involving modifications are mediated by three types of agents. Writer enzymes (modifying enzymes) introduce chemical modifications, such as a methyl group or acetyl group, onto DNA or histones. Reader proteins recognize the modifications and switch genes on or off. Eraser enzymes (de-modification enzymes) remove modifications once no longer needed (Figure 2). The collaboration of these three agents contributes to cellular memory that enables cells to maintain their own identity.<\/p>\n Figure 2. <\/span>Basic elements of the epigenetic control mechanism<\/span><\/strong>There are three key elements in the epigenetic control mechanism. DNA methylation enzymes and histone modification enzymes write modifications. DNA methylation-binding proteins and histone modification recognition proteins read modifications and switch genes on or off. DNA demethylation enzymes and histone de-modification enzymes erase modifications that are no longer required.<\/p>\n<\/div>\n Recent research has revealed that epigenetic abnormalities are involved in the mechanisms behind an assortment of diseases. There is a particularly strong association with cancer. For example, Helicobacter pylori<\/i> (H. pylori<\/i>) infection is regarded as the leading cause of gastric cancer; the infection results in chronic inflammation of the gastric mucosa, causing changes in the DNA methylation pattern. Scientists have also discovered cases in which methylation does not return to its original pattern even once H. pylori<\/i> has been eradicated, leaving the patient at a high risk of developing gastric cancer, and the degree of methylation is being applied to predicting the onset of the disease.<\/p>\n A number of epigenetic drugs have been developed. For example, when a cell becomes cancerous, changes may occur, such as an increase in methylation (suppression) of genes that control cell division or repair mutations; therapeutic drugs that control this process have been developed. Drugs that inhibit DNA methylation enzymes are effective in some patients with myelodysplastic syndromes (MDS; a condition sometimes described as pre-leukemia), for which there were hitherto hardly any effective drugs.<\/p>\n Drugs that target histone modification have also appeared on the scene. Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histones and inhibit transcription; in cancer cells, HDACs may be overactivated, silencing tumor suppressor genes. HDAC inhibitors, which block this phenomenon, have been approved for use against a number of blood cancers.<\/p>\n However, crucial issues still remain. DNA methylation enzymes and HDACs are enzymes that affect the function of many genes in the body. That means they act on not only target genes, but also other genes, and so side effects have been reported. There are also aspects where the mechanism of action has not been fully clarified; scientists know that they work, but do not yet have a clear picture of the reasons why. Epigenetic drug discovery also aims at a range of other diseases, but the development of technology for selectively targeting genes of interest is a major challenge.<\/p>\n The relationship between epigenetic abnormalities and diseases of the brain and nervous system is also attracting attention. There have been reports on patients with Alzheimer’s disease having reduced methylation levels in regulatory regions of specific genes. Accumulated data also suggests that epigenetic changes in the glial cells that support neurons are related to the progression of dementia and neurodegenerative disorders. Studies that reframe disorders of the brain from an epigenetic perspective are expanding rapidly.<\/p>\n In addition, regarding autism spectrum disorder (ASD), it has been reported that numerous mutations are found around genes that regulate the association of histones with DNA, and their functions. Furthermore, while DNA methylation normally works to suppress DNA sequences called transposons, scientists have pointed out derepression of transposons in ASD. Based on indirect evidence of this kind, many researchers believe that epigenetic abnormalities are, in some way, involved in the etiology of ASD.<\/p>\n Regarding the relationship between lifestyle diseases and epigenetics, there is a famous study focused on a historical event.<\/p>\n Toward the end of World War II, a Nazi Germany-imposed blockade on food supplies caused a severe famine in the western Netherlands. It became apparent that children born to mothers who were pregnant during this period frequently went on to develop diseases including obesity, hypertension, ischemic heart disease, and type 2 diabetes mellitus in adulthood. Scientists believe that epigenetic modification patterns altered as a result of their lacking adequate nutrition at the fetal stage, causing them to develop an energy-conserving metabolic profile, which persisted after birth. People who experienced famine while in the womb are also reported to have had reduced DNA methylation of the insulin-like growth factor 2 (IGF2) gene.<\/p>\n As well as being crucial to development and cell differentiation, epigenetics is also responsible for etching the impacts of lifestyle and environment onto the body. One of the best illustrations is the epigenetic clock, which is a major topic of discussion right now. Derived from the correlation between DNA methylation patterns at various locations on the genome and a person’s actual age and health condition, this tool makes it possible to estimate a person’s biological age. One could say that it visualizes the marks left on the genome (and eventually the body) by disease and lifestyle. For example, in patients who are positive for human immunodeficiency virus (HIV), the biological age estimated by the epigenetic clock tends to shift toward a older state than their actual age; in other words, that they appear to be aging faster.<\/p>\n Private sector services that use the epigenetic clock in lifestyle-related consultations have emerged, while DNA specimens left at crime scenes are being used to estimate the age of individuals connected to the case. Consideration is reportedly given to the application of the epigenetic clock by life insurance companies. Even though it remains unclear what individual methylation patterns mean in biological terms, we have obtained a useful yardstick with the aid of machine learning.<\/p>\n Attention has come to focus on the potential of epigenetic modifications as biomarkers, as typified by the epigenetic clock. Epigenetic patterns differ according to cell type, with each of the more than 200 human cell types—several thousand types, if you divide them into finer categories—having its own epigenome. The International Human Epigenome Consortium (IHEC), to which Japan contributes, was established to decode them. By putting in place “normal” reference data, it will become easier to develop technologies for identifying abnormal epigenetic patterns in patients’ cells.<\/p>\n While many differences in our characteristics and individual features are down to differences in the DNA forming the base of our makeup, it is not only our genes that determine our biological functions; epigenetics also has a major impact.<\/p>\n A familiar example of epigenetics can be found in calico cats (Figure 3). Calico cats have tricolored fur in white, orange, and black, and this is related to an epigenetic phenomenon called X chromosome inactivation in females (calico cats are nearly always female).<\/p>\n Figure 3. <\/span>The mechanism determining the patterns on calico cats<\/span><\/strong>The black and orange patches in a calico cat’s tricolored fur are caused by X chromosome inactivation involving epigenetic modifications. As the genes determining whether the fur will be black or orange are located on the X chromosome, only one of these colors appears in males, which have only one X chromosome. On the other hand, because females have two X chromosomes, they can possess the information for both orange and black, forming the basis of a calico cat’s fur. During early development, one of the two X chromosomes is chosen at random to be inactivated by means of epigenetic modification in each cell. Cells that express the orange gene produce orange pigment, while cells that express the black gene produce black pigment. Pigment cells then spread out across the surface of the body and occupy certain regions, forming different tricolor patterns in each individual. As the white color is due to the action of a different gene, it is unrelated to X chromosome inactivation.<\/p>\n<\/div>\n Of the genes that determine fur color, the gene responsible for white fur is located on an autosome, which is a chromosome present equally in male and female. On the other hand, the gene that switches the production of black (eumelanin) or orange (pheomelanin) pigment is located on X chromosome. As males have only one X chromosome, only one color will emerge, either orange or black. In addition to calico cats, tortoiseshell cats, which have bicolored fur in black and orange, are virtually all female for the same reason.<\/p>\n Although females have two X chromosomes, it is deleterious to have both of them active, so one of the X chromosomes is randomly chosen for inactivation at an early stage during development. Some areas become white due to the action of the gene located on an autosome, while the rest will become either orange or black, depending on which X chromosome is inactivated, thereby creating a tricolored pattern. In other words, the color of the pigmented parts of a calico cat’s fur is determined by chance through an epigenetic mechanism called random X chromosome inactivation. This is precisely why even genetically identical cloned cats will not have exactly the same tricolored fur pattern.<\/p>\n However, from the time the hypothesis of calico cat patterns was propounded in 1961 right through until the present post-genome era, the gene on the X chromosome had, for some reason, not been identified. Accordingly, I set out to identify the gene, with the cooperation of those around me.<\/p>\n The domestic cat (Felis catus<\/i>) diverged from the African wildcat (Felis lybica<\/i>) around 10,000 years ago. As the African wildcat is dark brown in color, bright orange is a newly emerged mutation. It occurred to me that in that case, we might be able to identify the gene if we looked for a mutation on the X chromosome found only in cats having orange fur. When we analyzed the genomic DNA of cats with various fur colors that we had collected in Fukuoka and compared their DNA sequences, we discovered a deletion of around 5,000 bases within a gene called ARHGAP36 on the X chromosome of cats with orange fur. Furthermore, when we compared our findings with the cat genome data available from the University of Missouri in the U.S., the presence or absence of the deletion coincided exactly with whether or not the cats had orange fur.<\/p>\n We then investigated the deleted region further and found that it was a DNA sequence called an ultraconserved element found across many animal species, including humans, mice, dogs, and chickens. Scientists believe that ultraconserved elements control gene expression; as calico cats lack this sequence, expression of the ARHGAP36 gene is dysregulated and the ARHGAP36 protein is overproduced. A larger amount of ARHGAP36 protein suppresses eumelanin synthesis, resulting in synthesis of more pheomelanin that gives orange color. Thus, after 60 years, we have shed light on the mechanism responsible for calico cats’ orange fur.<\/p>\n Epigenetics is a mechanism that changes the way genes are used, without changing the DNA sequence itself. The mechanism determines when and where genes are turned on or off by using DNA methylation to switch genes off, and also by finely controlling the switch by regulating the action of histones, the proteins around which DNA is wrapped. The crux of the matter is that even where genetic information is the same, gene function is influenced by environmental factors and life experiences. As such, epigenetics has become a major focus of research in many fields, including cancer, metabolic diseases, and other lifestyle diseases.<\/p>\n","protected":false},"author":2,"featured_media":2672,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[14],"tags":[109],"class_list":["post-2675","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicine","tag-calico-cat"],"acf":{"author":"composition by Rie Iizuka Epigenetics is a mechanism that changes the way genes are used, without changing the DNA sequence itself. The mechanism determines when and where genes are turned on or off by using DNA methylation to switch genes off, and also by finely controlling the switch by regulating the action of histones, the proteins around which DNA is wrapped. The crux of the matter is that even where genetic information is the same, gene function is influenced by environmental factors and life experiences. As such, epigenetics has become a major focus of research in many fields, including cancer, metabolic diseases, and other lifestyle diseases.<\/p>","person":[{"acf_fc_layout":"personcontent","personimg":2671,"personsholder":"University Professor and Professor Emeritus, Kyushu University","personname":"Hiroyuki Sasaki","persondetail":"Completed a PhD program at Kyushu University Graduate School of Medical Sciences in 1987. In 1993, he was appointed associate professor at Kyushu University Institute of Genetic Information. In 1998, he took up the post of professor at the National Institute of Genetics. He was appointed distinguished professor at Kyushu University Medical Institute of Bioregulation in 2010, and has held his current post since 2022. The focus of his research is epigenetics and genetics, and he is keen to convey the fascination of science. His hobbies are mountain climbing and visiting hot springs."}],"issue":2673,"custom_css":""},"_links":{"self":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2675","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/comments?post=2675"}],"version-history":[{"count":0,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2675\/revisions"}],"acf:post":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/issue\/2673"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media\/2672"}],"wp:attachment":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media?parent=2675"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/categories?post=2675"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/tags?post=2675"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":2661,"date":"2026-05-14T10:03:46","date_gmt":"2026-05-14T01:03:46","guid":{"rendered":"https:\/\/staging.healthist.net\/en\/?p=2661"},"modified":"2026-05-14T01:20:52","modified_gmt":"2026-05-13T16:20:52","slug":"delving-into-the-mysteries-of-soil-the-japan-soil-inventory-an-at-a-glance-guide-to-soil-distribution","status":"publish","type":"post","link":"https:\/\/healthist.net\/en\/nature\/2661\/","title":{"rendered":"Special Feature 1 \u2013 Delving into the Mysteries of Soil! <\/small>The Japan Soil Inventory: An at-a-glance guide to soil distribution"},"content":{"rendered":" In 2010, the National Institute for Agro-Environmental Sciences (now the National Agriculture and Food Research Organization; NARO) launched the Soil Information Web Viewer, enabling internet users to view a soil map of agricultural land in Japan online. Since 2017, a soil map covering virtually the whole of Japan, including non-agricultural land, has been available via NARO’s Japan Soil Inventory website (Figure 1). Japan’s soils are classified into 381 categories, and this website enables users to see at a glance which soil types are located in which areas.<\/p>\n Figure 1. <\/span>National soil map and distribution as a proportion of area (%)<\/span><\/strong>In the Japan Soil Inventory, one can view a soil map covering the whole of Japan, which was drawn up using the latest soil classification system (Comprehensive Soil Classification System of Japan: First Approximation). One can see that Andosols, which account for 31% of Japan’s total land area, are commonly located in the southern Hokkaido, northern Tohoku, Kanto, and Kyushu regions.<\/p>\n<\/div>\n The soil map that formed its basis was compiled via a survey program launched by the Ministry of Agriculture and Forestry (now the Ministry of Agriculture, Forestry and Fisheries) in the 1950s. Over a period of almost 20 years, from 1959 to 1978, the ministry conducted the Fundamental Soil Survey for Soil Fertility Conservation, with the aim of efficiently ensuring soil productivity and conserving soil fertility. Surveyors dug holes to a depth of 1 m every 500 m on agricultural land across the country and identified the properties of the soil. The survey data was then compiled and incorporated into maps. However, there were few opportunities for farmers to actually view the completed paper maps. They were not usually made available to the public, and producers could only get to see them if they went to the trouble of inquiring with the prefectural agriculture promotion agencies, so the reality was that farmers had no idea what kind of soil their land had. In addition, as the distribution of agricultural land has changed significantly since the survey was conducted, agricultural land is now also located in areas that were not surveyed at the time. Accordingly, the current database was produced after updating the data to include around 400,000 locations that were not surveyed at the time, on the basis of expert knowledge.<\/p>\n As can be surmised from the fact that the initiative was originally launched by the Ministry of Agriculture and Forestry, soil is a resource from which food production originates. For each type of soil, there are crops suited to its properties. The six main factors of soil formation are climate, vegetation, topography, parent rock (the rock from which the soil originates), time, and human activity. We can contribute to agriculture by conducting research to ascertain how these factors operate and thereby shed light on soil properties. I have heard that many of the users of the Japan Soil Inventory are agricultural promotion agencies, Japan Agricultural Co-operatives, and producers. There are actually cases in which, even when a crop is cultivated in the same way in neighboring fields, one field will yield a plentiful harvest, while the other yields nothing at all. This is because the soils are completely different, despite the fields’ proximity. There is tremendous significance in the fact that it has become easy to access the information needed to check soil conditions.<\/p>\n The soils shown in blue on the Japan Soil Inventory soil map indicate Lowland soils (Figure 2). As can be gathered from the fact that they are mainly distributed around rivers, the principal parent material of Lowland soils includes sediment deposited by river flooding. Lowland soils are classified into five subgroups and are generally known to be fertile soils, because the repeated addition of sediment from river floods keeps the parent material in a fresh state at all times, and they are also generally rich in nutrients. One can see that such soils are common in the major rice-producing areas of Niigata Prefecture, Akita Prefecture, and Yamagata Prefecture. Although the total area of Japan accounted for by Lowland soils is only around 14%, they account for about 70% of land used for paddy fields in Japan. This is because they are the optimal soils for rice cultivation—which requires the soil to be covered with water—as Lowland soils tend to be clay-rich and poorly drained, due to their high water table.<\/p>\n Figure 2. <\/span>Lowland soil (Collected in Takamatsu City, Kagawa Prefecture)<\/span><\/strong>Lowland soils are classified into five groups, one of which is Gray Lowland soils. There is a layer of iron mottling (soil with a reddish-brown mottled appearance resulting from the buildup of iron due to fluctuations in the water table) within 50 cm of the surface.<\/p>\n<\/div>\n The ability of a soil to nurture agricultural crops is called soil fertility, and this depends on how good or bad the soil is at retaining water and retaining nutrients (i.e. drainage, permeability, and nutrient retention capacity). The appropriate crops to produce differ according to the properties of the soil. For example, the reason why attempts to cultivate soybeans on land suited to paddy fields fail is that soybeans dislike water. If a farmer wishes to stop growing rice and use the land that was used for paddy fields as upland fields, they must first improve its drainage. Paddy fields with Lowland soil that have been covered in water often have a bluish color. This is because there is no oxygen in Lowland soil when it is covered in water, so the iron in the soil contains a high proportion of ferrous (divalent iron) ions (Fe2+<\/sup>). As Fe2+<\/sup> is pale green in color in an aqueous solution, paddy field soil is often bluish. As it dries out, oxygen spreads throughout the soil, turning the Fe2+<\/sup> ions into ferric (trivalent iron) ions (Fe3+<\/sup>), so the soil takes on a brown color.<\/p>\n So, what kind of soil is suitable for upland fields? In fact, Japan has a great deal of a type of soil that is rare worldwide: Andosols (Figure 3). Andosols account for as much as 31% of Japan’s total land area (the areas shown in bright brown on the soil map). Looking at all land on Earth, Andosols account for just 0.6%. As such, they truly are a soil characteristic of Japan.<\/p>\n Figure 3. <\/span>Andosol (Collected in Aya Town, Miyazaki Prefecture)<\/span><\/strong>Andosols are classified into six groups, one of which is Allophanic Andosols. Poorly crystalline clay minerals (allophane and imogolite) and humus have built up on a matrix of volcanic ejecta.<\/p>\n<\/div>\n It is precisely these Andosols that are suited to upland field cultivation. While they account for 31% of Japan’s total land area, that figure rises to around 47% when considered solely as a proportion of upland fields (ordinary fields, pastureland, and land under permanent crops). As they have good moisture retention capacity and permeability, the soil is soft and easy to plow.<\/p>\n But why do Andosols account for more than 30% of Japanese land area, when they make up less than 1% of all land on Earth? The reason lies in active volcanoes—that is to say, volcanoes that have erupted within the last 10,000 years and volcanoes that currently have active fumarolic activity. Andosols are soils formed from the deposition of volcanic ash. There are currently around 1,500 active volcanoes worldwide, as many as 111 of which are concentrated in Japan. The Japanese archipelago is located at a point where four oceanic and continental plates—the Pacific plate, the Philippine Sea plate, the Eurasian plate, and the North American plate—collide. Magma is formed when an oceanic plate sinks below a continental plate. The presence of so many active volcanoes is the reason why so much of Japan’s soil is made up of Andosols.<\/p>\n Japan’s Andosols are mainly located in the southern Hokkaido, northern Tohoku, Kanto, and Kyushu regions. It would be fair to say that this reflects the distribution of active volcanoes. The Japan Soil Inventory soil map shows that Andosols are located to the east of active volcanoes. This can be explained by the fact that volcanic ash emitted as a result of large-scale volcanic eruptions (eruptions in which the plume of ash reaches an altitude of 10,000 m) mainly travels and is deposited to the east of the volcano, due to the influence of winds called the westerlies. For example, the Andosols that make up a great deal of the soil surface in Tokyo, Kanagawa Prefecture, and other parts of the southern Kanto region were formed by the deposition of volcanic ash ejected during volcanic activity by Mount Fuji, Mount Hakone, and Mount Asama, among others.<\/p>\n As Andosols have many pores (holes or traces of plant roots) that formed during the process of the gradual deposition of volcanic ash, they drain very well. Another characteristic of soils derived from volcanic ash is their high content of active aluminum. Magma ejected by a volcanic eruption rapidly cools and decompresses, releasing the gas within the magma, which then forms volcanic ash and pumice containing a lot of bubbles. Rainwater flows into the bubbles in the volcanic ash after it reaches the ground, causing a great deal of aluminum—which does not normally dissolve very much—to leach out and bond with plant-derived organic matter in the soil. As a result, the soil gradually turns black in color.<\/p>\n The Japanese term for Andosol is kurobokudo<\/i>, which translates as “crumbly black soil.” It was in the wake of World War II that the English name was coined. When staff from the General Headquarters of the Supreme Commander for the Allied Powers carried out resource exploration and soil surveys of Japan’s territory, they were astonished to discover a type of black soil they had never seen before. Upon asking Japanese people what it was, they were told it was ando<\/i> (dark soil). Accordingly, they combined the Japanese word ando<\/i> with the suffix “sol,” which is derived from the Latin word solum<\/i>, meaning soil.<\/p>\n Whereas Andosols can now be described as fertile soils suited to upland field cultivation, they were once barren soils ill-suited to farming. This was because the active aluminum in which Andosols abound has a very powerful ability to absorb phosphate. Moreover, in humid climatic conditions such as those found in Japan, calcium and other minerals are lost from the soil when it rains, acidifying the soil. Phosphate ranks alongside nitrogen and potassium as one of the three macronutrients for crops. As it absorbs very strongly to active aluminum in the soil when it is in this acidic state, it cannot be absorbed by plant roots. As a result, crops do not thrive. On the Omiya Plateau during the Edo period (1603–1868), for example, farmers sought to overcome this problem by transporting rich, non-Andosol soil from riverbanks to improve the soil in their fields. They also supplemented the deficient phosphates by applying large quantities of organic fertilizer.<\/p>\n While both are black soils, this is something that differentiates Andosols from the Chernozems found across the huge wheat-producing area of Ukraine, where “Chernozem” means “black soil” in Russian. A byword for fertile soil, Chernozems are calcium-rich, neutral to mildly alkaline soils. As calcium forms loose bonds with plant-derived organic matter and builds up, the soil turns black. As calcium is a crop nutrient in its own right, it keeps the soil at a neutral pH level and provides an efficient supply of nutrients to crops.<\/p>\n Unlike Chernozems, acidic Andosols were barren soils. They were the bane of many producers’ lives. As many people will know from his poem Be Not Defeated by the Rain, poet and author of children’s stories Kenji Miyazawa provided agricultural guidance to farmers while cultivating his own fields. At Morioka Imperial College of Agriculture and Forestry (now the Faculty of Agriculture, Iwate University), he undertook soil research under the tutelage of Professor Toyotaro Seki. Professor Seki was one of the leading soil scientists in academic circles at the time, and served as the first president of the Japanese Society of Soil Science and Plant Nutrition. Most of the diluvial terraces in Iwate Prefecture are covered in Andosols, making the land acidic and barren. Accordingly, Kenji Miyazawa undertook research into a technique called acidity correction, to reduce the soil’s acidity. In his graduation thesis, entitled “The Value of Inorganic Elements in the Humus for Plants,” he reached the conclusion that soil-burning methods were means of turning Iwate’s Andosols into fertile soil. This shows how unsuitable Andosols were for agriculture back then, and how much improvement such soils required. It was after the war that the situation changed significantly. This is because phosphate-based chemical fertilizers in the form of calcium superphosphate and fused phosphate fertilizers became readily available.<\/p>\n Once chemical fertilizers entered widespread use, Andosols were increasingly used for upland field cultivation. As these soils are formed from volcanic ash, they do not contain any stones. They are also well-drained, making them suitable for growing root vegetables. The fact that wheat and soybeans are produced in the Andosols that stretch across the Tokachi Plain in Hokkaido can also be attributed to not only the climate conditions, but also the fact that wheat and soybeans do not require much water. In southern Kyushu, centered on Kumamoto Prefecture, production of the root vegetables such as sweet potato and daikon radish is flourishing in the area’s Andosol fields.<\/p>\n The first thing to assess when thinking about a nation’s food security is its soil resources. Japan was early in drawing up soil maps. The Meiji government invited German pedologist Dr. Max Fesca to Japan in 1882, and the Agronomic Map of the Kai-Province<\/i> was completed under his guidance three years later. Charting the soils of Kai Province (modern-day Yamanashi Prefecture), this was Japan’s first soil map to be drawn up from a scientific viewpoint. In addition, a preliminary soil map of Japan was exhibited at the 1889 International Exposition in Paris to tremendous acclaim.<\/p>\n It is thanks to the efforts of such pioneers that we were able to complete the Japan Soil Inventory, and we have supplied the soil map data in the Inventory to other websites. For example, there is a website that calculates how much CO2<\/sub> is stored in soil. Soil carbon storage, in which carbon absorbed from the atmosphere is locked in the earth in the form of soil organic matter, plays a major role in measures against global warming. Our data is used by this website, as well. Japan Soil Inventory data is also used to calculate the optimal quantity of fertilizer. The amount of fertilizer leached is determined by soil temperature and moisture content. There are a number of websites that calculate the appropriate quantity of fertilizer, which use our soil property data as well as data for moisture content and soil temperature estimated from air temperature and the like. We ourselves have created an app for visualizing element supply from various organic amendments, which is used by agricultural promotion agencies, among others. In around 70 cases where this app has been used to manage fertilizer use over the last three years, the effective use of manure and other organic soil amendments has succeeded in roughly halving chemical fertilizer use. As well as cutting costs, this is reducing the burden on the environment.<\/p>\n However, soil does change in response to such factors as land use and natural disasters. In some places the layer of black soil that was as much as 80 cm deep 50 years ago has been washed away, exposing the next layer down. In other words, more than 1.5 cm of soil has been lost per year in those places. In recent years, the whole of Japan has experienced torrential rain due to climate change, so the soil has likely changed quite a lot as well. While we have scaled down our work, we are still gathering the latest soil data from 1,000–2,000 sites per year (Figure 4). In addition, today we are able to use supercomputers and AI to estimate the process of changes in soil properties, which could not be assessed using older technologies. Making full use of these new technologies to analyze the latest survey results, we are continuing our efforts to further increase the accuracy of the Japan Soil Inventory soil map.<\/p>\n Figure 4. <\/span>Conducting a soil survey<\/span><\/strong>Soil is surveyed by digging a hole to a depth of 1 m. Part of the process involves creating a solidified specimen (soil monolith) of the cross-section of soil in its natural state. NARO’s Natural Resources Inventory Museum exhibits around 100 soil monoliths, which are around 20 cm wide and 1 m tall.<\/p>\n<\/div>\n What kinds of soil exist in which locations? A website called the Japan Soil Inventory provides answers to questions just like these. It is a digitized version of the Soil Information Web Viewer developed by the National Agriculture and Food Research Organization, which covers the whole of Japan, and it provides users with an at-a-glance understanding of the distribution of soil across the country, which has 381 different types of soil when soil on non-agricultural land is also included. As soil has a major influence on agricultural crop production, understanding which soils are suitable for cultivation is absolutely crucial. Ensuring the stable availability of soil resources is an issue that should also be top of mind from the perspective of a nation’s food security.<\/p>\n","protected":false},"author":2,"featured_media":2657,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[18],"tags":[],"class_list":["post-2661","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-nature"],"acf":{"author":"composition by Takeaki Kikuchi","intro":" What kinds of soil exist in which locations? A website called the Japan Soil Inventory provides answers to questions just like these. It is a digitized version of the Soil Information Web Viewer developed by the National Agriculture and Food Research Organization, which covers the whole of Japan, and it provides users with an at-a-glance understanding of the distribution of soil across the country, which has 381 different types of soil when soil on non-agricultural land is also included. As soil has a major influence on agricultural crop production, understanding which soils are suitable for cultivation is absolutely crucial. Ensuring the stable availability of soil resources is an issue that should also be top of mind from the perspective of a nation’s food security.<\/p>","person":[{"acf_fc_layout":"personcontent","personimg":2656,"personsholder":"Senior Researcher, National Agriculture and Food Research Organization (NARO)","personname":"Yusuke Takata","persondetail":"Graduated from Obihiro University of Agriculture and Veterinary Medicine in 2001. In 2007, he successfully completed a doctoral program at Kyoto University’s Graduate School of Agriculture. After holding a Research Fellowship for Young Scientists at the National Institute for Agro-Environmental Sciences and then serving as a senior researcher at the same institution, he took up his current post in 2016. That same year, he received the Japan Award for Young Agricultural Researchers from the Ministry of Agriculture, Forestry and Fisheries for compiling a digital soil map and a distribution map showing the concentration of radioactive materials in agricultural land."}],"issue":2638,"custom_css":""},"_links":{"self":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2661","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/comments?post=2661"}],"version-history":[{"count":0,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2661\/revisions"}],"acf:post":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/issue\/2638"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media\/2657"}],"wp:attachment":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media?parent=2661"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/categories?post=2661"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/tags?post=2661"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":2658,"date":"2026-05-14T10:02:08","date_gmt":"2026-05-14T01:02:08","guid":{"rendered":"https:\/\/staging.healthist.net\/en\/?p=2658"},"modified":"2026-05-14T01:20:45","modified_gmt":"2026-05-13T16:20:45","slug":"delving-into-the-mysteries-of-soil-the-diverse-microorganisms-in-soil-that-support-healthy-rice-plant-growth","status":"publish","type":"post","link":"https:\/\/healthist.net\/en\/nature\/2658\/","title":{"rendered":"Special Feature 1 \u2013 Delving into the Mysteries of Soil! <\/small>The diverse microorganisms in soil support healthy growth of rice plants"},"content":{"rendered":" “Rice is grown by the inherent soil productivity, while wheat\/barley are grown with commercial fertilizers.” That was the saying back in the days when commercial fertilizers were more expensive than now. The “inherent soil productivity” refers to the innate soil fertility. Experiments conducted from the early 20th century until after World War II revealed that decline in the rice yields was much smaller than those of wheat\/barley when fertilizers were not applied.<\/p>\n In Japan, most rice for consumption is cultivated in paddy fields, with only very little cultivation in upland fields. The high soil fertility of paddy fields is closely related to the functions of microorganisms in the soil (Figure 1).<\/p>\n Figure 1. <\/span>Microbial functions in soil<\/span><\/strong>The three plant macronutrients are nitrogen, potassium, and phosphorus, but plants cannot absorb nutrients in organic form. In addition to transforming macronutrients from organic to inorganic forms, microorganisms serve as microbial biomass by storing and supplying nutrients.<\/p>\n<\/div>\n Rice plants need not only sunlight and water from irrigation and\/or rain, but also nutrients from fertilizers to thrive in paddy fields. Almost all the nutrients that rice and all other plants can absorb are in inorganic forms. Microorganisms in the soil decompose organic matter, such as animal and plant residues, as well as compost, and transform them into inorganic forms.<\/p>\n The three major macronutrients for plants are nitrogen, potassium, and phosphorus, which are the primary elements of fertilizer. Nitrogen is particularly important; plants absorb ammonium and nitrate as nitrogen sources which are transformed from nitrogen in soil organic matter (organic nitrogen) by microorganisms. Rice plants absorb mainly ammonium as the nitrogen source which is derived from not only fertilizer but also organic nitrogen in the soil. Ammonium derived from organic nitrogen accounts for around half of the total nitrogen uptake by rice plants. The role of microorganisms in converting organic nitrogen to inorganic forms is therefore crucial.<\/p>\n Microbial cells as well as human cells contain various nutrients. This role of nutrient reservoir is called “microbial biomass” and has been regarded as important in recent years. After the death of microorganisms in the soil, nitrogen, phosphorus, potassium, and other substances stored in their cells are released (Figure 2). Ammonium is mainly produced via amino acids by the decomposition of proteinaceous nitrogen derived from microbial cells and then absorbed by rice plants. Bacterial members in the genus Bacillus<\/i>—to which Bacillus subtilis<\/i> and the variant used for making fermented soybeans, Bacillus subtilis<\/i> var. natto<\/i>, also belong—contribute to this mineralization process in paddy field soil. Although the content of microbial biomass nitrogen is low, accounting for just a few percent of the total nitrogen content in soil, it turns over actively and therefore plays a key role as a source of inorganic nitrogen.<\/p>\n Figure 2. <\/span>The role of microbial biomass<\/span><\/strong>Nitrogen (N), phosphorus (P), and potassium (K) are released following the death of microorganisms in the soil. Nitrogen and phosphorus are then transformed into inorganic forms by microorganisms.<\/p>\n<\/div>\n As potassium does not form organic compounds, unlike nitrogen and phosphorus, it has long been believed that rice plants absorb water-soluble potassium via a mechanism that does not involve microorganisms. However, our research has revealed that potassium in microbial cells is also released after they die, like nitrogen and phosphorus. In addition, in the paddy fields without application of potassium fertilizer, we observed that the amount of potassium derived from microorganisms was higher than the amount of potassium attributed to the mechanism in which microorganisms were not involved. This indicates that microbial biomass plays an important role as a source of potassium in the fields.<\/p>\n Paddy fields are flooded and rice transplanting begins around May. The flooded conditions last for about 100 days and then the paddy fields are drained before harvest. Functions and activities of microorganisms change during this cycle, which contribute to maintaining paddy field soil suitable for rice growth (Figure 3).<\/p>\n Figure 3. <\/span>Microbial reduction of soil<\/span><\/strong>Anaerobic microorganisms cause various substance transformations in the anoxic soil after being covered with floodwater. In addition, cyanobacteria inhabiting floodwater synthesize nitrogen compounds such as ammonia from atmospheric nitrogen (nitrogen fixation).<\/p>\n<\/div>\n When the paddy fields are covered with floodwater, less oxygen enters the soil from the atmosphere. As aerobic microorganisms that use oxygen for metabolism consume oxygen by respiration, the soil other than the surface layer beneath the floodwater gradually becomes anoxic (lacking in oxygen).<\/p>\n As a result, microorganisms carry out metabolism by fermentation and anaerobic respiration, which uses oxygen-containing substances such as nitrate, manganese and iron oxides, sulfate, and CO2<\/sub> instead of molecular oxygen. Since less energy is obtained from the fermentation and anaerobic respiration than from the aerobic respiration, the decomposition rate of organic matter decreases, which causes accumulation of organic nitrogen in the soil, and consequently the content of organic nitrogen increases. The findings that the organic nitrogen content in soil is higher in paddy fields than in upland fields indicate the high fertility of paddy fields, although the amount varies depending on the type of soil.<\/p>\n Removal of oxygen from oxides (reduction) through the fermentation or metabolism by microorganisms leads to positive changes in the soil. For example, iron is present as ferric (trivalent) iron in oxic soils such as in upland fields. Phosphorus, an important nutrient, is combined with ferric iron to form ferric phosphate, which does not readily dissolve in water and therefore can hardly be absorbed by plants. However, as ferric iron is reduced to ferrous (divalent) iron in paddy fields, the bound phosphate dissolves in water and can be absorbed by rice plants.<\/p>\n Reduction of soil also influences the concentration of hydrogen ions (pH) in the soil. The optimal pH for paddy rice is weakly acidic to neutral. It was reported that production of hydrogen ions associated with decomposition of organic matter and consumption of hydrogen ions through iron reduction are balanced and pH settles to neutral as the reduction process progresses, even in highly acidic or alkaline soils.<\/p>\n Furthermore, the reduction of soil has been believed to be involved in the mechanisms that enable continuous cropping of rice in paddy fields, unlike upland rice cultivation. This has been mainly because of the suppression of aerobic pathogens such as filamentous fungi, but questions remain. This is because lotus root and arrowhead suffer continuous cropping disorder due to filamentous fungi, though these crops are also grown in flooded fields.<\/p>\n So, why paddy rice does not suffer continuous cropping disorder? To prevent root rot, rice plants transport oxygen taken up from the leaves and stems of rice plants above the ground to roots and a small amount of oxygen leaks out through the roots. Based on this phenomenon, we are studying to test two hypotheses: either free radicals<\/span> produced by the oxidation of ferrous iron have a fungicidal effect, or aerobic protozoa prey on pathogens around rice roots.<\/p>\n Aside from reduction of soil, there is another microbial function unique to flooded paddy fields, for which cyanobacteria, blue-green algae, inhabiting floodwater are responsible. Cyanobacteria grow photosynthetically and synthesize nitrogen compounds such as ammonia from atmospheric nitrogen (nitrogen fixation). The amount of nitrogen fixed by cyanobacteria in a single cropping season of rice was estimated to be 26 kg\/ha in an experiment. Given that rice plants require about 100 kg\/ha nitrogen from fertilizers, it can be said that the role of cyanobacteria is large.<\/p>\n On the other hand, microorganisms do not necessarily always have a positive effect on rice plants. Japanese soil scientists have found solutions for the problems that negatively impact the growth of rice plants by elucidating dynamics of the components and microbial functions in the soil over the years. For example, in the late 1920s and early 1930s, when commercial fertilizers were still expensive, the poor efficacy of ammonium sulfate as a nitrogen fertilizer became a problem. As described above, oxygen consumption by microorganisms in the soil was active just after flooding paddy fields, but it stabilizes after a while; the uppermost surface layer of the soil is oxidized with the oxygen diffused from floodwater. When a nitrogen fertilizer such as ammonium sulfate is applied to the surface layer, microorganisms called nitrifying bacteria oxidize the ammonium to nitrate. As soil particles are negatively charged, also negatively charged nitrate cannot be absorbed to soil particles and immediately moves to the lower, reduced layer of the soil. In the reduced layer, denitrifying bacteria immediately use the nitrate for anaerobic respiration to obtain energy by oxidizing organic matter and transform nitrate to nitrogen gas. In other words, the expensive nitrogen fertilizer is applied with effort, but it is converted into nitrogen gas and escapes into the atmosphere.<\/p>\n Once this mechanism has been clarified, a method for incorporating the fertilizer into the reduced lower layer or all layers has been developed to retain ammonia and nitrogen fertilizer can be applied effectively.<\/p>\n In addition, sulfate-reducing bacteria produce hydrogen sulfide, which is potentially harmful to the growth of rice plants, by reducing sulfate ion of ammonium sulfate. However, hydrogen sulfide is combined with ferrous iron produced by iron reduction and detoxified as iron sulfide. Therefore, paddy fields with sufficient iron are not a problem, but a phenomenon called “autumn decline” occurs in paddy fields, where the content of iron in the soil is originally low or iron levels have greatly decreased by heavy leaching as in degraded paddy fields. A representative symptom of autumn decline is that rice plants thrive through the summer and deteriorate in autumn before harvest. Autumn decline can be remedied by applying a soil amendment containing iron, deep plowing to put the iron from the bottom layer back to the upper layer, and oxidizing the soil by drainage.<\/p>\n Conversely, if there is too much iron in soil, the rice plants absorb an excessive amount of ferrous iron, causing poor growth. This phenomenon is rarely seen in Japan and occurs in paddy fields with a high iron content in soil such as the fields located in tropical basins; in some cases, the entire harvest is lost. The countermeasures are to oxidize the soil by drainage, but large-scale agricultural infrastructure work such as the laying of culverts to manage water flow is required.<\/p>\n Application of rice and wheat\/barley straw as fertilizer has been employed for a long time. If a large amount of fresh, unfermented straw is applied, the decomposition process of organic matter by microorganisms fails to progress smoothly, and organic acids, intermediate metabolite products, may accumulate in the soil, causing rice growth inhibition. Organic matter is quickly degraded to CO2<\/sub> by microorganisms under oxic conditions, but under anoxic conditions, it is ultimately metabolized into CO2<\/sub> and methane via intermediate metabolites including fatty acids such as acetic acid, propionic acid, and butyric acid, as well as aromatic carboxylic acids. In particular, it has been reported that aromatic carboxylic acids have a major impact on rice plant growth, even at low concentrations, and are often produced in paddy fields in warm regions. Currently, to prevent these metabolites from accumulating, straw is composted before use or it is incorporated into the soil before flooding of the field for allowing decomposition.<\/p>\n Methane is the final decomposition product in the metabolic process described above and becomes a problem. While methane does not affect growth of rice plants, it has a stronger greenhouse effect than CO2<\/sub> and has therefore emerged as a major environmental problem in recent years. In particular, in Japan, methane emissions from rice cultivation account for the largest share of total emissions derived from human activities, at 44%. Methane is produced by anaerobic microorganisms called methanogens inhabiting paddy field soil and is emitted via aerenchyma in rice plants. To suppress activities of methanogens, the following countermeasures are being implemented: oxidizing the soil by the midseason drainage with temporary draining paddy fields around at the maximum tillering stage of rice or the intermittent irrigation with repeated flooding and draining every few days, and application of composted straw.<\/p>\n In addition, the oxidized part of paddy field soil is also inhabited by methane-oxidizing bacteria that oxidize methane to CO2<\/sub>. We are conducting a collaborative research project with research institutions to identify highly active methane-oxidizing bacteria and utilize them to mitigate methane emission. One might wonder whether this approach will increase CO2<\/sub> emissions. In fact, most of the methane comes from CO2<\/sub> taken up by rice plants during photosynthesis. Therefore, even if methane-oxidizing bacteria convert methane to CO2<\/sub>, the balance comes out even and it is unlikely to lead to an increase in CO2<\/sub> emissions.<\/p>\n Interestingly, microorganisms inhabiting paddy field soil, as mentioned above, are stably present without large fluctuation in the composition and abundance even when paddy fields are drained and the soil is oxidized. When the drained paddy fields are flooded again in the following year, microorganisms start to work again. However, if paddy fields are converted to upland fields and oxic soil conditions sustain for more than a year or two, microorganisms specific to paddy field soil decrease in the abundance and the composition also changes. Therefore, it is necessary to consider the changes in microorganisms when paddy-upland rotation, interconversion between paddy fields and upland fields for certain periods, is implemented to reduce rice production.<\/p>\n While we have already made progress in unraveling the mechanisms behind various phenomena caused by microorganisms in paddy field soil, there still remain many unknowns, including the functions of individual microorganisms. In order to sustain stable production of rice, a staple food in not only Japan but also the rest of Asia, it is important to identify microorganisms and elucidate the more detailed mechanisms. We will continue to undertake basic research using DNA\/RNA analysis in addition to conventional culture techniques, and work on environmental conservation such as mitigation of methane emission as well as improving growth of rice plants.<\/p>\n Rice is a wetland plant. Growing rice in paddy fields can suppress growth of upland weeds and facilitates soil managements. Paddy field soil generally shows higher fertility than upland field soil, supporting stable rice yields under low fertilization conditions. A combination of several factors resulted in the development of rice cultivation in paddy fields in Japan. The high fertility of paddy fields is supported by various functions of microorganisms in the soil. They decompose organic matter in the soil and produce inorganic nutrients requisite for growth of rice plants. On the other hand, emission of methane, one of the decomposition products of organic matter, has become an environmental problem. Mitigation of methane emission is a pressing issue since the gas has a stronger greenhouse effect than CO2<\/sub>.<\/p>\n","protected":false},"author":2,"featured_media":2664,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[18],"tags":[],"class_list":["post-2658","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-nature"],"acf":{"author":"composition by Yumi Ohuchi Rice is a wetland plant. Growing rice in paddy fields can suppress growth of upland weeds and facilitates soil management. Paddy field soil generally shows higher fertility than upland field soil, supporting stable rice yields under low fertilization conditions. A combination of several factors resulted in the development of rice cultivation in paddy fields in Japan. The high fertility of paddy fields is supported by various functions of microorganisms in the soil. They decompose organic matter in the soil and produce inorganic nutrients requisite for growth of rice plants. On the other hand, emission of methane, one of the decomposition products of organic matter, has become an environmental problem. Mitigation of methane emission is a pressing issue since the gas has a stronger greenhouse effect than CO2<\/sub>.<\/p>","person":[{"acf_fc_layout":"personcontent","personimg":2650,"personsholder":"Professor, Graduate School of Bioagricultural Sciences, Nagoya University","personname":"Susumu Asakawa","persondetail":"Holds a Ph.D. in agriculture. Graduated from the Department of Agricultural Chemistry, Faculty of Agriculture, the University of Tokyo in 1985. After working as a researcher at the Kyushu National Agricultural Experiment Station, Ministry of Agriculture, Forestry and Fisheries, he became an associate professor at the Graduate School of Bioagricultural Sciences, Nagoya University in 2001 and took up his current post in 2013. In 2021, he was also appointed to Vice Director of Nagoya University Library. He specializes in the ecology of microorganisms inhabiting paddy field soil ecosystems, methanogenic archaea, methane-oxidizing bacteria, etc."}],"issue":2638,"custom_css":""},"_links":{"self":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2658","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/comments?post=2658"}],"version-history":[{"count":0,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2658\/revisions"}],"acf:post":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/issue\/2638"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media\/2664"}],"wp:attachment":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media?parent=2658"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/categories?post=2658"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/tags?post=2658"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":2646,"date":"2026-05-14T10:01:39","date_gmt":"2026-05-14T01:01:39","guid":{"rendered":"https:\/\/staging.healthist.net\/en\/?p=2646"},"modified":"2026-05-14T01:20:04","modified_gmt":"2026-05-13T16:20:04","slug":"delving-into-the-mysteries-of-soil-the-worlds-diverse-soils-are-closely-linked-to-human-activity","status":"publish","type":"post","link":"https:\/\/healthist.net\/en\/nature\/2646\/","title":{"rendered":"Special Feature 1 \u2013 Delving into the Mysteries of Soil! <\/small>The world’s diverse soils are closely linked to human activity"},"content":{"rendered":" I am sure that everyone played with soil when they were a child. Sometimes, in my university classes, I ask the students, “When you painted pictures as a child, what color was the soil?” Students from the Kanto region are likely to reply that it was dark brown or black. As I am from Osaka, I tend to associate soil with the color ocher. Thus, while soil is a very familiar ecosystem, if we take color as just one example, its properties differ considerably from one region to another.<\/p>\n Before explaining about soils of the world and their food productivity, I would like to touch upon the fact that each country’s culture is heavily influenced by its soil.<\/p>\n Ancient China had a philosophical system called Wuxing (the Five Elements); the Four Gods that appear within this system are said to be divine creatures that preside over the cardinal directions. The Azure Dragon of the East, the White Tiger of the West, the Vermilion Bird of the South, and the Black Tortoise of the North respectively take the colors blue, white, red, and black. One could go so far as to describe these four colors as the primary colors of soil.<\/p>\n The birthplace of Chinese culture is a region called the Central Plains, located around the middle to lower reaches of the Yellow River. If we look at China’s territory with the Central Plains as the midpoint, we can see that the soil to the east is blue, that to the west is white, that to the south is red, and that to the north is black. I was amazed to discover that this grand philosophy established more than two thousand years ago has its roots in the actual color of the soil found in each region.<\/p>\n The Mesopotamian civilization developed in a region that stretches from the modern countries of Iran and Iraq all the way to Syria. Among the legends of that time is a tale in which mistreatment of the soil caused a god to appear from the soil and scatter salt all around, rendering the soil too saline for anything to grow. This is thought to refer to a phenomenon called salinization, in which the evaporation of moisture in soil causes salt to accumulate on the soil’s surface and become increasingly concentrated, which inhibits plant growth. This means that, even back in those days, people understood the phenomenon of salt damage and its root cause, and incorporated it into their tales in an instructive manner.<\/p>\n Produced during the Nara period (710–784 CE) by various provinces at the instruction of Empress Genmei, Japan’s surviving Fudoki<\/i> manuscripts are geographical descriptions recording such matters as each area’s place names and produce, including records of the productivity of local soil. While modern Japan offers few opportunities to consider land productivity, in days of yore, the productivity of the soil was a matter of tremendous concern to the government of the day from the perspective of establishing an appropriate taxation system. In that sense, I believe that soil science is the very foundation of managing a nation.<\/p>\n Now that I have explained the sociocultural aspects, let us look at soil around the world from a scientific viewpoint.<\/p>\n Soil science as a modern science began with research conducted in the latter half of the 19th century by Russian geologist and geographer Vasily Dokuchaev. Dokuchaev classified the soils of the world on the basis of his belief that soil properties were determined by a combination of five formation factors: geology (the parent rock and sediment), climate, biology, topography, and time.<\/p>\n Today, the world’s soils are broadly classified into 32 groups in the World Reference Base for Soil Resources (WRB), which is endorsed by the International Union of Soil Sciences (IUSS) and widely used by such bodies as the Food and Agriculture Organization of the United Nations (FAO). Under the U.S. Department of Agriculture (USDA) Soil Taxonomy, they are classified into 12 orders.<\/p>\n If we look at a distribution map of the latter, we can see that, as expected, similar soils are formed in places with similar formation factors such as climates and topography (Figure 1). Let us look at soils around the world.<\/p>\n Figure 1. <\/span>Global soil distribution map<\/span><\/strong>This is the taxonomy of the world’s soils developed by the USDA. In addition to the 12 types of soil that function as areas where food production is actually possible, there are three types of areas without soil: rock, shifting sand, and ice.<\/p>\n<\/div>\n The Eurasian Steppe, which includes Ukraine and Kazakhstan, the North American prairies of Canada and the U.S., and Argentina’s extensive Pampas all have a semiarid steppe climate and fertile black soil (called Mollisols in the USDA taxonomy). “Molli” is derived from the Latin word mollis<\/i>, meaning soft, while “sol” is derived from solum<\/i>, meaning soil. Soft black soil contains an abundant accumulation of mineral nutrients and organic matter called humus, which is formed when plants, for the most part, are decomposed and transformed by microorganisms. Mollisol is the most highly productive soil in upland farming. It would be no exaggeration to say that, as some of the foremost wheat-growing areas, these regions produce virtually all the world’s bread and pasta. The world’s major powers are located in these regions, and many wars have been fought with the aim of seizing this land. Both Napoleon and Hitler invaded what was then Russia, in an effort to capture Ukrainian territory.<\/p>\n On the plateaus of Central Africa and South America, one sees a lot of red soil with a low level of productivity, due to “rust” formed by the oxidation of iron in the soil as a result of the humid climate.<\/p>\n In the course of the soil’s exposure to rain and wind for millions of years, the three major plant nutrients—nitrogen, phosphates, and potassium—are washed away, along with other elements such as calcium and magnesium, whereas iron becomes insoluble after reacting with oxygen and builds up in the soil. This is why the soil turns red. Soil and plants have a cyclical system in which plants absorb nutrients in the soil and produce starches (organic matter) via photosynthesis, before returning to the soil when they die. However, red soil (Oxisols) has a relatively high iron content, because the nutrients are washed away. One might go so far as to liken this soil to the leftovers from making stock.<\/p>\n One hardly sees any examples of this kind of old red soil in Japan. As Japan has volcanoes, as well as precipitous mountains prone to erosion, its soil rarely stays in the same place for long periods.<\/p>\n What Japan has in abundance is volcanic ash soil and young acidic soil of the kind found on plains formed by the repeated flooding of rivers. Japan’s soil is new, with even the oldest dating back only tens or hundreds of thousands of years, while the andosols that are widely distributed around the country are about 10,000 years old, at most. One can see just how young that is if one compares it to the soil in Scotland, which dates back 500 million years.<\/p>\n Desert soil is the richest in nutrients. This might seem surprising, but deserts contain an abundance of minerals, including not only sodium, but also phosphates, potassium, and calcium, because the lack of rainfall means nutrients do not get washed away.<\/p>\n The Mesopotamian and Egyptian civilizations succeeded in achieving high levels of food production by using water channeled from major rivers (irrigation), along with abundant sunshine and the intrinsically fertile soil of the desert.<\/p>\n However, using the wrong irrigation method causes salt damage. Adding water to land that did not originally have groundwater creates an artificial aquifer in the layer below the surface soil in which crops are grown. When this happens, a phenomenon called capillary action occurs, in which the groundwater percolates up into the surface soil. In the process of the water percolating up, salt and other substances dissolve, and the salt concentration gradually increases. The moisture evaporates, but the salt and other substances remain in the soil, turning it a whitish color.<\/p>\n What happens when crops are cultivated in soil with high salt levels? I often use the example of nukadoko<\/i>, a bed of rice bran used in Japanese cuisine for pickling vegetables. When vegetables are grown in soil with a high salt content, the moisture in the vegetables leaches out like in pickles, causing them to shrivel and leaving them unable to absorb nutrients via their roots, so they die. This accumulation of salt in soil is called salinization and is one type of soil degradation. Salinization often occurs in desert land, but it can even occur in semiarid areas such as Ukraine, ruining precious fertile land, so proper management is required.<\/p>\n We have conducted surveys of agricultural land across the globe, but irrigation is not a simple solution, as the situation differs from one place to another. Even where soils appear at first glance to be the same, an elevation difference of just 10 cm or so can be crucial, with land at the higher elevation being fine, but salt rising to the surface in the lower-lying land. It is not easy to wash away this salt once it has emerged, and doing so costs huge sums of money.<\/p>\n In Kazakhstan, I witnessed a case in which salinization caused farmland soil to degrade in just 30 years.<\/p>\n Between the 1960s and the 1990s, Kazakhstan forcibly increased agricultural output while it was still part of the territory of the Soviet Union. Motivated by the dramatic shrinkage of the Aral Sea, we went to Kazakhstan, and it really did seem as though the land was being consumed. The Syr Darya, a river whose source is located in the Tianshan Mountains, flows into the Aral Sea, which is a huge lake that can be seen on any globe. However, it has now dried up almost entirely. As a result of huge amounts of water being drawn from the Syr Darya to irrigate Kazakhstan’s desert, water stopped flowing into the Aral Sea and it gradually shrank. People familiar with the situation locally had predicted this result, but boosting output was the top priority under the five-year plans of the former Soviet Union. When salt damage made the land impossible to farm, people ended up abandoning it and moving to farmland elsewhere. The abandoned land could only be used as pasture for sheep and goats. In quite a few cases, even that pastureland turned into semi-desert once the grass dwindled.<\/p>\n This kind of land consumption did not necessarily occur because this area was part of what was the Soviet Union; the same phenomenon also occurs in the U.S. and Australia, so I believe that appropriate land management is a global issue that continues today.<\/p>\n Whereas Kazakhstan was an example of salinization, in Niger, we addressed the problem of wind erosion (Figure 2). Wind erosion was also depicted as the social background to John Steinbeck’s The Grapes of Wrath<\/i>. This is a problem in which wind blows soil away, reducing the fertility level of the remaining soil.<\/p>\n Figure 2. <\/span>Fallow bands in fields in Niger<\/span><\/strong>Alternating fallow and cultivated bands are arranged in a single field to prevent soil from being dispersed by the wind. Understanding and acceptance by local people are also essential.<\/p>\n<\/div>\n Niger’s fields were becoming progressively desertified. The farmers there cultivate pearl millet (Pennisetum glaucum<\/i>), but strong winds blow the soil around, dispersing the nutrients. Accordingly, the farmers undertook shifting cultivation by rotating cultivated land and fallow land every few years, but population growth meant they faced the need to increase output.<\/p>\n We first visited the area and conducted a survey, which resulted in our research team proposing a method called the Fallow Band System. The key to this method is creating both fallow and cultivated bands within a single field. Although they are called fallow bands, the method actually just involves allowing grass to grow; the soil and nutrients blown around by the wind catch on the grass and fall to the base of plants, preventing nutrients from being lost from the soil. We created a system that would enable the farmers to make good use of the land by using the fallow band as a cultivated field and the cultivated field as a fallow band the following year.<\/p>\n However, even though we devised the idea for the fallow band system, we had to undertake repeated on-site surveys and experiments in order to find the optimum method for the location in Niger. After gathering particles scattered by the wind, and investigating what types and quantities of particles blew around at what level of wind speed, and what length of grass would be needed to trap them, we found a balance that would maintain productivity while avoiding damage to the soil. Even if we think our method is good, local people will not be satisfied with it if it requires too much extra effort or imposes excessive costs, and they will not adopt the system. Accordingly, we explore support methods based on a hands-on approach, while observing the environment and the reactions of the local farmers.<\/p>\n When it comes to Japan, I believe there is little cause for concern about soil degradation. Although cases of salinization do occur in greenhouse cultivation, Japan’s high rainfall means that soil can recover, and with rice paddies at least, there is no possibility of wind erosion.<\/p>\n While rice paddies require considerable effort, they give rise to little soil degradation, making them a sustainable method compared with upland farming. At present, paddy rice cultivation is principally carried out in South, Southeast, and East Asian countries. This region accounts for about half the world’s population, but just 12% or so of its land area. From this, one can understand that paddy cultivation is a highly productive agricultural method capable of supporting a large number of people per unit of land area. I believe this farming method should be passed on to future generations in Japan and other Asian countries.<\/p>\n However, there is no single universally applicable method that is beneficial for soil and suitable for every part of the globe. Techniques for preventing soil degradation and maintaining the soil environment differ from one environment to another. Even the question of what constitutes healthy soil to start with differs according to the ecosystem. In order to keep the world’s soils healthy, I believe it is crucial to understand soil diversity and explore optimal solutions that take into account not only the ecosystem, but also sociocultural characteristics.<\/p>\n The reason why we provide support for conserving agricultural land and strengthening ecosystem functions in various parts of the world is because we feel a sense of crisis regarding the fact that soil is being used up. Soil is key to nutrient cycling in ecosystems and supports almost all forms of life on Earth. Those familiar with the field of soil science believe that our planet’s soil is capable of meeting the food needs of around 10 billion people. However, this is only possible if the soil is managed with proper and optimal care, avoiding wars or regional conflicts which directly reduce farming areas, and indirectly trigger or accelerate soil degradation, leading to a drastic decline in current and future food production. In fact, there are major regional differences in production capacity, and the problem of how to distribute food still remains. Alternatively, technologies such as plant factories that do not rely on soil might advance, but the situation in which we are currently reliant on soil for at least 95% of our food production is unlikely to change any time soon. I believe we need to properly manage land to prevent its depletion, ensuring that farmland is not abandoned and land capable of being used for food production is not repurposed for other uses.<\/p>\n Those of us involved in the field of soil science are also engaged in awareness activities across the globe, focusing on soil and soil science. The IUSS has designated the period from 2025 to 2034 as the Decade of Soil Sciences for Sustainable Development, and is undertaking activities aimed at promoting a deeper understanding of soil among a larger number of people.<\/p>\n Soils around the world each have their individual characteristics, which are influenced by such environmental factors as climate, topography, parent material, biology and time. The black soil mainly found extensively across the Eurasian Steppe and other regions with a semiarid steppe climate is soft, rich in both organic matter and mineral nutrients, and highly productive. The lack of rain in deserts means that nutrients do not get washed away, so the soil is rich in minerals. However, some land has been degraded by human activity; for example, irrigation has caused salinization in Kazakhstan, while overcultivation in Niger has been responsible for wind erosion. Scientists are engaged in ongoing efforts to understand the diversity of soils and explore measures that also take into account sociocultural characteristics.<\/p>\n","protected":false},"author":2,"featured_media":2645,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[18],"tags":[108],"class_list":["post-2646","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-nature","tag-rice"],"acf":{"author":"composition by Rie Iizuka","intro":" Soils around the world each have their individual characteristics, which are influenced by such environmental factors as climate, topography, parent material, biology and time. The black soil mainly found extensively across the Eurasian Steppe and other regions with a semiarid steppe climate is soft, rich in both organic matter and mineral nutrients, and highly productive. The lack of rain in deserts means that nutrients do not get washed away, so the soil is rich in minerals. However, some land has been degraded by human activity; for example, irrigation has caused salinization in Kazakhstan, while overcultivation in Niger has been responsible for wind erosion. Scientists are engaged in ongoing efforts to understand the diversity of soils and explore measures that also take into account sociocultural characteristics.<\/p>","person":[{"acf_fc_layout":"personcontent","personimg":2644,"personsholder":"Professor Emeritus and Senior Visiting Researcher, Institute of International Affairs, Aichi University","personname":"Takashi Kosaki","persondetail":"Graduated from Kyoto University. Holds a Ph.D. in Agriculture. After holding positions including research scientist at the International Institute of Tropical Agriculture (IITA) and professor at Kyoto University, he took up his current post in 2023. His areas of interest are soil science and global environmental science. Addressing a diverse array of soil degradation problems, principally in Africa and Asia, he is continuing his research into establishing sustainable land use methods, and has also been working on soil and environmental education in recent years. He has served as president of both the Japanese Society of Soil Science and Plant Nutrition and the International Union of Soil Sciences. Among the awards he has received are the Japan Prize of Agricultural Science and the International Soil Science Award of the Soil Science Society of America."}],"issue":2638,"custom_css":""},"_links":{"self":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2646","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/comments?post=2646"}],"version-history":[{"count":0,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2646\/revisions"}],"acf:post":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/issue\/2638"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media\/2645"}],"wp:attachment":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media?parent=2646"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/categories?post=2646"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/tags?post=2646"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":2640,"date":"2026-05-14T10:00:02","date_gmt":"2026-05-14T01:00:02","guid":{"rendered":"https:\/\/staging.healthist.net\/en\/?p=2640"},"modified":"2026-05-14T01:19:49","modified_gmt":"2026-05-13T16:19:49","slug":"delving-into-the-mysteries-of-soil-earths-soil-is-the-foundation-that-supports-biological-activity-but-what-actually-is-it","status":"publish","type":"post","link":"https:\/\/healthist.net\/en\/nature\/2640\/","title":{"rendered":"Special Feature 1 \u2013 Delving into the Mysteries of Soil! <\/small>Earth’s soil is the foundation that supports biological activity, but what actually is it?"},"content":{"rendered":" As the basis of food production, soil is closely connected to our biological activity, but most people have little idea of what soil actually is.<\/p>\n For example, even the Moon has powdery sand. Unlike soil on Earth, the sand on the Moon does not contain clay. This is because there is no water. Almost all clay is produced by the chemical weathering of minerals in rock; when the component minerals that have leached out of rock become concentrated, they form microparticles in which silicon, aluminum, oxygen, and hydrogen are packed closely together like rugby players in a scrum (Figure 1). At no more than 0.002 mm, these particles are extremely small, but such fine sand does not exist on the Moon. The Moon has sand with particles about the same size as flour, formed from rocks that have shattered during the repeated process of expansion and contraction resulting from their being heated by the Sun, followed by cooling. However, as there are no living things on the Moon, this sand does not develop a complex structure like our planet’s soil, which has the remains of dead flora and fauna mixed into it, along with microorganisms. Mars used to have water, which reacted with iron in its rocks to form rust, so the planet’s surface became covered in red sand, but it, too, has no organic matter. In other words, the sand on both the Moon and Mars consists of inorganic particles (regolith) that are the result of the weathering of rocks, without the involvement of biological activity.<\/p>\n Figure 1. <\/span>The structure of clay<\/span><\/strong>The structure of a clay mineral (mica, in this example) consisting of silicon and aluminum. An oxide of aluminum (Al) is sandwiched between two layers of silicon (Si) forming a structure reminiscent of rugby players in a scrum. Potassium ions (K+<\/sup>) and cesium ions (Cs+<\/sup>) that are similar in size to the spaces between the silicon layers cling tightly to them, increasing viscosity.<\/p>\n<\/div>\n Earth originally had no soil, just like the Moon and Mars. However, after components of rock that dissolved in rainwater became concentrated and formed microparticles, organisms began to become active, and the surface environment of Earth gradually started to change. This was 500 million years ago, 4.1 billion years after Earth’s birth. Microorganisms and plants grew and died. The majority of their remains returned to the atmosphere in the form of CO2<\/sub>, but about 1% remained in the ground without decomposing. This tiny amount of residue built up over thousands, then tens of thousands of years to form soil containing organic matter (Figure 2).<\/p>\n Figure 2. <\/span>The composition of soil<\/span><\/strong>Dead leaves fall onto the ground (❶), where they are broken down by a diverse array of microorganisms. Most are released into the atmosphere in the form of CO2<\/sub>, but the minute quantity of microorganism “leftovers” becomes soil (❷, ❸).<\/p>\n<\/div>\n In soil science, soil is defined as a substance with a complex structure that consists of a mixture of mineral components produced from the disintegration of rocks, organic matter from organisms, and innumerable microorganisms. As biological activity also takes place in soil, it could be described as the very essence of an environment, in which formation and decomposition are constantly taking place at the same time.<\/p>\n On Earth, the term “soil” principally refers to the layer from the surface to a depth of around 1–2 m. Generally speaking, this is the extent of the soil layer containing a mixture of weathered rock and the remains of dead flora and fauna. Soil is the site of activity for microorganisms, worms, and plant roots, as distinct from the rock mass (bedrock) below it (Figure 3).<\/p>\n Figure 3. <\/span>Earth’s structure and its soil layer<\/span><\/strong>Soil is a resource that exists on only a very thin part of Earth’s surface.<\/p>\n<\/div>\n NASA is undertaking research into the creation of soil on Mars and the Moon, with an eye to humankind living in space one day. In space, where there are no living organisms, it will be necessary to create a cyclical process by first introducing and cultivating resilient plants such as mosses, then having microorganisms break their remains down after they die, and mixing the organic matter with minerals.<\/p>\n However, there are no microorganisms in space. Having obtained material developed by NASA to replicate the sand on Mars and the Moon, we, too, are conducting research using moss that survived in space (as proven by a team led by Professor Tomomichi Fujita of Hokkaido University) to find out what kind of microorganisms need to be added in order to produce soil, but it is not easy. The biggest reason why nobody has managed to establish a technology for producing soil artificially from scratch is the complexity of the microorganisms in soil. Scientists say there are at least 10 billion bacteria in a single tablespoon of soil, and at least 10,000 different species of microorganisms. It is only when those 10,000 or more different microorganisms are collaborating while undertaking their own specialized tasks that the remains of dead plants can decompose. We are still studying what kind of microorganisms we need to select. It is still very rare to find bacteria like Bacillus subtilis<\/i> var. natto<\/i> and Lactobacillus<\/i> that can be removed on their own from the natural world and used for human purposes—such bacteria account for less than 1% of all bacterial species.<\/p>\n Another crucial feature of soil is its structure. Soil is not merely a mass of small particles; it is a three-dimensional structure produced as a result of the secretions of microorganisms, clay minerals, and organic matter becoming entangled and forming links to each other. This is called an aggregated structure. Within that aggregated structure are numerous gaps that retain air and water (Figure 4). This structure develops further through worms and other soil fauna eating soil and then excreting it as feces. Soil in which this mechanism is widespread achieves a good balance between drainage and moisture retention capacity. If microorganisms that can only survive inside this structure are removed from soil, they cease to function as they should.<\/p>\n Figure 4. <\/span>Aggregated structure<\/span><\/strong>The difference between soil with an aggregated structure and soil without. The soil on the left has maintained its aggregated structure and is soft, with an abundance of gaps between the particles. In the soil on the right, the aggregated structure has broken down, leaving it hard and densely packed. This structural difference has a major impact on plants growth.<\/p>\n<\/div>\n Looking at the potting soil sold at garden centers, people tend to think that humans are able to artificially produce soil. However, this is actually nothing more than a blend created by gathering soil that already existed. Nobody has managed to make soil artificially as yet.<\/p>\n Soil and sand are important resources. For example, high-purity “eleven-nine” (i.e. a purity level of 99.999999999%) silicon dioxide is required for the silicon wafers used in semiconductor production. As the silicon in Japanese sand is bonded to aluminum, making it unsuitable for semiconductor production, Japan is reliant on imports of high-purity sand from China. No matter how advanced our semiconductor manufacturing technology is, we face the problem that the sand used as a raw material does not exist in Japan. On the other hand, sand is also consumed in large quantities as a construction material. Sand is produced every year, as mountain rocks weather and are deposited in rivers and along coasts, but the demand for concrete, which is made from sand, is twice that amount, with the result that supply cannot keep up.<\/p>\n In Japanese soil, meanwhile, aluminum is bonded to silicon, and a huge amount of energy is required to separate them. This is why we cannot manufacture aluminum from domestic raw materials alone, and are dependent on imported bauxite to meet most of our needs. The fact that Japan recycles a large volume of aluminum cans is closely connected to this lack of domestic aluminum resources.<\/p>\n Soil’s greatest role as a resource is in food production. Somewhere in the region of 95–98% of the food we eat originates from soil. As well as vegetables, of course, even beef traces its origins back to the soil, as cows eat grass, which grows in soil. The plant factories that have become the focus of attention of late have the advantage of allowing water and nutrients to be reused, but they require a great deal of energy and the crops that can be cultivated in them are limited to high-priced leafy salad vegetables. Open-field agriculture that enables us to harness sunlight, rain, and microbial action is essential to support our staple daily diet.<\/p>\n Japan depends on imports for most foodstuffs, which at the same time means it is reliant on overseas soil in this regard, too. The temporary suspension of French fry sales at fast food outlets a few years ago was symbolic of this issue. The potatoes we eat every day in Japan are supported by the fertile soil of Canada and the U.S. If that region is hit by drought, flooding, or insufficient sunlight, crop yields will fall, leading to the risk of French fries disappearing from menus.<\/p>\n The same applies to dairy farming. People tend to think of Hokkaido when dairy products are mentioned, but much of the feed consumed by dairy cows is imported from overseas. If a forest fire breaks out in Canada’s permafrost zone and the smoke leads to insufficient sunlight during its short summer, grass production on its southern prairies will fall. Further south, corn and soybeans will not grow even in the fertile soil of the U.S. if there is a shortage of water. Environmental changes of this kind are directly linked to dairy farming in Japan, and will lead to rises in the prices of cheese and butter. In other words, Japanese dining tables are closely connected to the soil environments of far-off lands.<\/p>\n According to researchers, the fertile black soil used as agricultural land across the globe increases by just 1 cm or so every 100 years—in other words, it hardly increases at all during the span of a human life. On the other hand, black soil is rapidly being lost as a result of overcultivation and excessive development, as well as deforestation. Much of the wheat used in Japan is imported from countries such as Canada and the U.S. Until around a century ago, a thick layer of this fertile black soil lay beneath the grasslands of that region. However, plowing of the land to turn it into fields for wheat and corn caused the black soil to decrease due to wind erosion and decomposition, and scientists say it is now less than half as thick as it used to be. As soil’s resilience cannot be seen from the surface, desertification—the process in which soil degradation causes yields to gradually decrease—progresses before we know it. It only becomes apparent when yields fall, but in quite a few cases, recovery is difficult once that resilience has been used up.<\/p>\n Furthermore, North America is a water-scarce region, so groundwater is pumped up for agricultural use, but as groundwater in areas that were formerly on the sea floor has a high salt content, accumulation of salt in the topsoil leads to salinization, which inhibits plant growth and can cause plants to wither and die. Studies have shown that salt accumulation causes an area of farmland equivalent to that of Iwate Prefecture to fall into disuse every year—this equates to one soccer pitch every 15 seconds. The fertile soil that nature has built up over such a long period is being used up to produce our food.<\/p>\n The deforestation of the Amazon rainforest is another serious problem. Rich virgin forest is increasingly being replaced by agricultural land consisting of red soil with few nutrients. Cattle farmed there are imported into Japan, along with pigs and chickens fed on corn and soybeans grown there. The deforestation of the Amazon rainforest is connected to our food system all the way over here in Japan. Tropical rainforests have also been cleared in Southeast Asia, so that corn and other crops could be cultivated on the fertile topsoil, which has a thickness of just 3 cm or so. As a result, only yellow, clay-rich soil remains. This has caused a vicious circle in which neighboring areas of tropical rainforest are cut down, leading to a situation in which the inability to sustainably manage the soil results in the loss of places where people can live.<\/p>\n Since establishing the Soil Conservation Service (renamed the Natural Resources Conservation Service in 1994) in 1935, the U.S. Department of Agriculture has rolled out a variety of measures. China, too, has stressed the importance of black soil from the perspective of ensuring food safety, dubbing it the “giant panda of cultivated land,” and enacted the Black Soil Protection Law in 2022. Across the globe, people are recognizing that the question of how to maintain fertile black soil is an issue of virtually equal importance for a nation to that of how to protect its territory.<\/p>\n In Japan’s case, although our country is deemed to have a low food self-sufficiency rate, we at least have ample rice production capacity.<\/p>\n As Japan has a temperate climate with high rainfall, the progressive weathering of rock creates an abundance of clay-rich soil. It is a favorable environment on a global scale. Thanks to this soil, Japan has had a ceramic culture since ancient times. The Jomon period (c. 12,000–2,300 BCE) saw a culture of boiling food begin to develop, with people boiling acorns to remove the tannins before eating them, as well as using fish to create hot pot dishes. This has also influenced Japanese people’s preference for soft foods.<\/p>\n In addition, our mountainous country with few plains has a long tradition of cultivating rice on its very limited supply of flat ground. What has made this possible is the supply of nutrient-rich water flowing down from the mountains and channeled through a network of irrigation and drainage canals with a total length of 400,000 km—about the same as the distance from Earth to the Moon. We take for granted the sight of drooping ears of rice in autumn, but it is only thanks to an environment blessed with fertile soil and abundant water that we can enjoy it.<\/p>\n Japan’s agriculture is said to be at an overwhelming disadvantage compared with other countries in terms of costs and scale, but its strength is sustainability. Whereas the history of rice production in California dates back only 100 years or so, rice cultivation in Japan has been going on for thousands of years. While Japan has only a small area of agricultural land, with many mountains and rivers, rain and snow falling on the mountains supply nutrients to the soil every year.<\/p>\n As mentioned above, both dairy farming and fast food in Japan can place a burden on the soil in other parts of the world. To put it another way, increasing sustainable agriculture in Japan will increase our food supply without imposing a burden on other countries’ soil. Innovation will be required to enable us to sustain such agricultural methods, and we should each consider where and in what soil our food is produced.<\/p>\n Soil is a complex structure composed not only of minerals released by the weathering of rocks on Earth’s surface, but also of water, air, organic and inorganic matter, and microorganisms. Formed over long periods of time under the influence of climate, topography, and living organisms, among others, soil is a living system that governs ecosystems, supports biological activity, and plays an essential role in our lives as a place where food is produced. However, it has deteriorated significantly as human activity has intensified, and is also affected by climate change. People are now becoming aware of a crucial question: how can we maintain Earth’s soil?<\/p>\n","protected":false},"author":2,"featured_media":2636,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[18],"tags":[107],"class_list":["post-2640","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-nature","tag-agriculture"],"acf":{"author":"composition by Rie Iizuka","intro":" Soil is a complex structure composed not only of minerals released by the weathering of rocks on Earth’s surface, but also of water, air, organic and inorganic matter, and microorganisms. Formed over long periods of time under the influence of climate, topography, and living organisms, among others, soil is a living system that governs ecosystems, supports biological activity, and plays an essential role in our lives as a place where food is produced. However, it has deteriorated significantly as human activity has intensified, and is also affected by climate change. People are now becoming aware of a crucial question: how can we maintain Earth’s soil?<\/p>","person":[{"acf_fc_layout":"personcontent","personimg":2635,"personsholder":"Unit Leader, Soil Homeostasis Research Unit, Fukushima Institute for Research, Education and Innovation (F-REI)","personname":"Kazumichi Fujii","persondetail":"Soil scientist. Born in 1981 in Toyama Prefecture. After successfully completing a doctoral program at Kyoto University’s Graduate School of Agriculture, he received a Ph.D. in Agriculture. After holding positions including Senior Researcher at the Forest Research and Management Organization’s Forestry and Forest Products Research Institute, he took up his current post in March 2025. With his trusty trowel in hand, he travels throughout Japan and across the globe to conduct research ranging from the permafrost of the Canadian Arctic to the tropical rainforests of Indonesia. His book Tsuchi: Chikyū saigo no nazo<\/i> [Soil: Earth’s last mystery] (Kobunsha Shinsho) was awarded the seventh Kawai Hayao Prize for social sciences and humanities, while Tsuchi to seimei no 46 oku nen shi<\/i> [The 4.6-billion-year history of soil and life] (Kodansha) received the 41st Kodansha Science Publication Award. His other books include Daichi no 5 oku nen<\/i> [500 million years of earth] (Yama-kei Publishers). He has also made many appearances in the media."}],"issue":2638,"custom_css":""},"_links":{"self":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2640","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/comments?post=2640"}],"version-history":[{"count":0,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2640\/revisions"}],"acf:post":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/issue\/2638"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media\/2636"}],"wp:attachment":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media?parent=2640"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/categories?post=2640"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/tags?post=2640"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":2623,"date":"2026-02-15T13:55:34","date_gmt":"2026-02-15T04:55:34","guid":{"rendered":"https:\/\/staging.healthist.net\/en\/?p=2623"},"modified":"2026-03-10T19:16:21","modified_gmt":"2026-03-10T10:16:21","slug":"special-feature-1-the-impact-of-mitochondria-cancer-cells-suppress-t-cells-by-means-of-mitochondrial-hijack","status":"publish","type":"post","link":"https:\/\/healthist.net\/en\/medicine\/2623\/","title":{"rendered":"Special Feature 1 – The Impact of Mitochondria <\/small>Cancer cells suppress T cells’ function by means of mitochondrial “hijack”"},"content":{"rendered":" I have reported that mitochondria in cancer cells are transferred into surrounding T cells, where they inhibit T cells’ function as immune cells and, as a result, suppress the effects of cancer immunotherapy.<\/p>\n I was originally a clinician specializing in lung cancer. During my time in that field, I saw firsthand how the effects of gefitinib (brand name: Iressa) differed from one patient to another, and learned that EGFR gene mutations had been found in tumors with a marked response. As I had seen for myself the major differences in the effects of cancer immunotherapy, and data indicative of this point had emerged in a number of articles as well, the question of why such variations occurred lingered powerfully in my mind.<\/p>\n Immune checkpoint inhibitors were first commercialized in the early 2010s. Nivolumab (brand name: Opdivo) went on sale in 2014, with its range of indications expanding thereafter. However, even here, the effects varied from one patient to another, so I embarked on research aimed at eliminating the questions I had had since my days as a clinician.<\/p>\n When I first began my cancer immunity research, I belonged to a laboratory researching regulatory T cells, so I was able to pursue studies using human specimens. I believe this to be one reason why my later articles met with favorable evaluation. By the time I left that laboratory to pursue independent research, a fair amount of time had passed since nivolumab’s launch and there had been quite a few studies on the differences in its effects, as well as efforts to explore blood biomarkers for measuring those differences. As such, I wondered whether there might be a research topic with greater originality.<\/p>\n At any rate, it was just then I heard about mitochondrial dysfunction in the T cells of cancer patients, and about the possibility of mitochondrial transfer. In addition, one of my friends was a researcher working on clonal hematopoiesis, and the fact I had often heard him talk about his work was also a catalyst for my decision to focus on gene mutations in T cells surrounding cancer cells. Clonal hematopoiesis is the phenomenon in which hematopoietic (blood-forming) cells with gene mutations proliferate vigorously, and may eventually lead to leukemia and other diseases.<\/p>\n As might be expected, most research focused on DNA in the cell nucleus rather than mitochondria. Numbering anywhere from hundreds to thousands in a single cell, mitochondria are a hindrance to what is termed genomic (nuclear DNA) analysis, so data relating to them were often discarded. It was perhaps fortunate for me that I myself had limited knowledge of mitochondria, as I decided to try analyzing mitochondrial DNA and, when I began my observations, I discovered the same DNA mutations in T cell mitochondria as in cancer cell mitochondria. That was back in 2021.<\/p>\n In an experiment, we stained cancer cell mitochondria red and T cell mitochondria green. When we cultured these cells together, the T cell mitochondria turned yellow. The yellow is created by the mixture of red and green. In this situation, both types of mitochondria coexisted, but some cells turned completely red. The fact that they turned red means we can say that the mitochondria in the T cells were replaced by those of the cancer cells (Figure 1). Our initial hypothesis that mitochondria might be transferred grew closer to certainty, as we observed that the cancer cells and surrounding T cells shared the same mutations.<\/p>\n Figure 1. <\/span>Mitochondrial transfer<\/span><\/strong>The red mitochondria from the cancer cells move into the T cells and mix with the green mitochondria, turning them yellow; in some cases, the green mitochondria are replaced by red.<\/p>\n<\/div>\n So, how does this mitochondrial transfer occur?<\/p>\n There are two main types of mitochondrial transfer (Figure 2). In the first method, a cell comes into contact with a recipient cell and grows a tube-like structure (tunneling nanotube, or TNT) through which the mitochondria travel. In the second method, mitochondria enter exosomes or other extracellular vesicles secreted when the cell fragments, and travel in these. There also appear to be cases in which macrophage-like cells grow tubes through which they send mitochondria into cancer cells. Perhaps because of such observations, there were many reports suggesting that cancer was activated by the supply of something from the surrounding cells to the cancer, whereas reports indicating transfer from cancer cells to surrounding cells were not predominant.<\/p>\n Figure 2. <\/span>Mechanism of mitochondrial transfer<\/span><\/strong>TNT extend from both T cells and cancer cells, through which mitochondria are transferred; mitochondria also transferred via extracellular vesicles.<\/p>\n<\/div>\n However, we did not imagine that cancer cells and their mitochondrial DNA would harbor mutations of some kind. Mutation is a phenomenon principally found in cancer cells; if the same mutation is found in a cancer cell and a T cell, it is only natural to conclude that the mutation originated in the cancer.<\/p>\n If a supply of normal mitochondria from surrounding T cells were beneficial to cancer cells, the mitochondrial DNA of cancer cells should be wild-type, but around 40% of the actual specimens showed high-frequency mutations in the mitochondrial DNA of cancer cells.<\/p>\n Mitochondria are transferred from cancer cells to T cells and vice versa, but we observed that few of the mitochondria transferred from normal cells to cancer cells survived. This might be because they are exposed to substantial oxidative stress within the cancer cells.<\/p>\n The hardest part of this study was demonstrating why mitochondria in T cells are replaced by those from cancer cells and why such a process can occur.<\/p>\n One conceivable reason is the powerful oxidative stress within cancer cells. Under normal circumstances, mitochondria are eliminated by means of mitophagy (mitochondrial autophagy) when subject to oxidative stress. However, we hypothesize that the fact that cancer cell mitochondria survive amid the powerful oxidative stress in those cells means that those mitochondria are resistant to oxidative stress, and that mitophagy is inhibited in cancer cells.<\/p>\n We also believe that when these resistant mitochondria are transferred to surrounding T cells, a mitochondrial “hijack” occurs. That is to say, even if normal mitochondria are eliminated through mitophagy, causing their numbers to decline, the mitochondria derived from cancer cells survive and replace the normal mitochondria.<\/p>\n Once the normal mitochondria are replaced, T-cell function dramatically declines, causing the T cells to age and become unable to survive for long. The drop in the effectiveness of cancer immunotherapy in this situation has been confirmed in experiments using specimens from both mice and humans. In addition, when we examined specimens from patients who had received immune checkpoint inhibitor therapy without undergoing chemotherapy, we found that the effectiveness of cancer immunotherapy did not last long in patients whose cancer cells harbored mitochondrial DNA mutations, and that their survival rates also fell (Figure 3).<\/p>\n Figure 3. <\/span>Association between immune checkpoint inhibitor effectiveness and mitochondrial DNA mutations<\/span><\/strong>The duration of response in patients treated with anti-PD-1 therapy was significantly shorter in the group with mitochondrial DNA mutations.<\/p>\n<\/div>\n This study also showed that mutated cancer cell mitochondria are transferred to surrounding T cells, where they replace the original mitochondria and consequently reduce the effectiveness of cancer immunotherapy. However, we feel that there are still a number of mysteries surrounding the relationship between mitochondrial mutations and cancer.<\/p>\n First of all, there is the question of whether mitochondrial DNA mutations are beneficial to cancer cells.<\/p>\n Some previously reported studies have focused on cells in which mitochondrial DNA mutations have been induced. In essence, they suggested that the mutation of mitochondrial DNA increases oxidative stress within the cell, making metastasis more likely. We, too, conducted experiments using these cells, as well as in mice, and did indeed observe that cells with mutations in their mitochondrial DNA were more prone to metastasize. However, at the same time, cancer cell growth slows considerably. One could say that this is a natural consequence of the fact that mitochondria are responsible for energy production in cells. Although slower growth is a negative phenomenon for cancer cells, it does, on the other hand, have a positive aspect in terms of making metastasis easier. The emergence of mutations in mitochondrial DNA is probably disadvantageous from the perspective of cancer cell growth and proliferation, but even so, we are left with the question of why mitochondria with mutations become predominant.<\/p>\n For example, if there were 1,000 mitochondria in a lung epithelial cell, at least initially only one would carry a mutation—in other words, one in 1,000. This abnormal mitochondrion should be removed by means of mitophagy, so it is inconceivable that it could take over the cell; however, in cancer cells, such mitochondria go on to predominate.<\/p>\n A phenomenon called the Warburg effect was reported around 100 years ago. This is the observation that, whereas ordinary cells produce adenosine triphosphate (ATP) via mitochondrial respiration in an oxygen-rich environment, cancer cells use the glycolytic pathway rather than mitochondrial respiration, for some reason, even in oxygen-rich environments.<\/p>\n The glycolytic pathway is a primitive method of producing ATP, with a production efficiency less than one-fifteenth that of mitochondrial respiration. However, it may have advantages, namely a rapid reaction rate and the generation of nucleic acids and lipids in the ATP production.<\/p>\n I stated above that, as a result of the self-cleansing system that is mitophagy being inhibited and ceasing to function in cancer cells, it became impossible to eradicate mutated mitochondria. However, mitochondrial mutations themselves might actually benefit cancer cells through such aspects as the speed of the energy production and the generation of other substances. No clear answers have emerged as yet.<\/p>\n Besides this issue, there are no hotspots for mitochondrial DNA mutations. The term “hotspot” refers to DNA regions where mutations are concentrated. In the context of cancer mutations, it means that once a mutation arises in a region advantageous to proliferation, similar mutations will swiftly increase. There are hotspots in the EGFR and KRAS genes, which promote cell proliferation and are known to be associated with cancer. If mitochondrial DNA mutations conferred an advantage to cancer cells, one would expect mutation hotspots, but mitochondrial DNA mutations are comparatively evenly distributed.<\/p>\n We do not currently know what impact each individual mutation in the mitochondrial DNA of T cells has. Accordingly, although we reported that there were mutations when compared with the wild type, one cannot deny the possibility that there is no functional impact, even if mutations are actually present.<\/p>\n In this report, we stated that the mitophagy function of T cells was inhibited and that mutated mitochondria came to predominate. But the question is, how is that function inhibited?<\/p>\n We reported that mitophagy does not readily occur even when mitochondria from cancer cells enter T cells, whereas the original T cell mitochondria are affected by mitophagy because they are normal, and, as a result, mitochondria derived from cancer cells become predominant in environments with strong oxidative stress. In our article, we were able to present data on this phenomenon early on, but we still do not understand why this phenomenon occurs, and the full range of specific molecules involved remains unknown. We are currently exploring potential factors.<\/p>\n In our report, we obtained our findings by observing human specimens, with a focus on mitochondria, but I believe there are various ways in which we could develop upon this work, such as examining whether mitochondrial DNA transfer from cancer cells occurs in other immune cells. We hope that future research, from the perspective of mitochondria harboring cancer cell-derived DNA mutations, will expand in ways that enhance the effectiveness of cancer immunotherapy.<\/p>\n The mechanisms by which cancer cells transfer mitochondria into T cells and replace the T cells’ healthy mitochondria are being elucidated. A subsequent study is now starting to reveal the specific mechanisms involved. At the same time, fresh puzzles have come to light. For example, if mitochondrial DNA mutates, energy production within cells naturally diminishes, slowing the growth of the cancer cells and thus disadvantaging them. As a number of other questions have yet to be explained, research into mitochondria derived from cancer cells continues to warrant close attention.<\/p>\n","protected":false},"author":2,"featured_media":2622,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[14],"tags":[106],"class_list":["post-2623","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicine","tag-regulatory-t-cells"],"acf":{"author":"composition by Rie Iizuka The mechanisms by which cancer cells transfer mitochondria into T cells and replace the T cells’ healthy mitochondria are being elucidated. A subsequent study is now starting to reveal the specific mechanisms involved. At the same time, fresh puzzles have come to light. For example, if mitochondrial DNA mutates, energy production within cells naturally diminishes, slowing the growth of the cancer cells and thus disadvantaging them. As a number of other questions have yet to be explained, research into mitochondria derived from cancer cells continues to warrant close attention.<\/p>","person":[{"acf_fc_layout":"personcontent","personimg":2621,"personsholder":"Professor, Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University","personname":"Yosuke Togashi","persondetail":"After graduating from the Medical Science Division at Kyoto University’s Faculty of Medicine in 2006, he joined Sumitomo Hospital. In 2009, he became a physician at Kyoto University Hospital. In 2011, he was appointed an assistant professor at Kyoto University’s Graduate School of Medicine. In 2012, he entered the doctoral program at Kindai University’s Graduate School of Medical Sciences, successfully completing it early in 2015. He subsequently served as an assistant professor at Kindai University’s Faculty of Medicine and, after holding a Japan Society for the Promotion of Science Research Fellowship for Young Scientists, as a researcher at the National Cancer Center Japan. He was then appointed as a division head at Chiba Cancer Center Research Institute before taking up his current post in 2021. Since September 2024, he has concurrently served as a professor in the Department of Respiratory Medicine at Okayama University Hospital."}],"issue":2593,"custom_css":""},"_links":{"self":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2623","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/comments?post=2623"}],"version-history":[{"count":0,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/posts\/2623\/revisions"}],"acf:post":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/issue\/2593"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media\/2622"}],"wp:attachment":[{"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/media?parent=2623"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/categories?post=2623"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/healthist.net\/en\/wp-json\/wp\/v2\/tags?post=2623"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}},{"id":2617,"date":"2026-02-09T10:49:43","date_gmt":"2026-02-09T01:49:43","guid":{"rendered":"https:\/\/staging.healthist.net\/en\/?p=2617"},"modified":"2026-03-10T19:00:46","modified_gmt":"2026-03-10T10:00:46","slug":"special-feature-1-the-impact-of-mitochondria-aiming-to-extend-healthy-life-expectancy-by-delaying-age-related-functional-decline","status":"publish","type":"post","link":"https:\/\/healthist.net\/en\/medicine\/2617\/","title":{"rendered":"Special Feature 1 – The Impact of Mitochondria <\/small>Aiming to extend healthy life expectancy by delaying age-related functional decline"},"content":{"rendered":" The eukaryotic cells in mammalian bodies contain not only a nucleus, which encloses genes within the nuclear membrane and manages genetic information, but also a number of structures called organelles, which include mitochondria, the Golgi apparatus (organelles that transport proteins by binding them to sugars), and lysosomes (organelles that break down unnecessary substances and waste products in the cell). Of these, mitochondria specialize in producing energy for biological activity.<\/p>\n The genetic information in the mitochondrial DNA (mtDNA) present in mitochondria is transcribed into messenger RNA (mRNA) and translated within the mitochondria. Failure of this translation mechanism has adverse impacts on organs with a large number of mitochondria, such as the brain, heart, and muscles, which can result in a variety of conditions referred to as mitochondrial diseases, including stroke, cerebral ataxia, cardiomyopathy, external ophthalmoplegia, and weakness of the muscles in the limbs.<\/p>\n If mitochondria become dysfunctional, nuclear DNA is also affected, impairing the mechanism whereby lysosomes—which could be described as the recycling centers of cells—break down unnecessary substances, damaged organelles, and waste products.<\/p>\n By engaging in crosstalk and rigorously controlling each other, the mitochondria, cell nucleus, and lysosomes maintain homeostasis within the cell. The relationship between these three elements is also connected to the link between mitochondria and aging.<\/p>\n We know that, generally speaking, mitochondrial function declines with age. As this decline progresses, what was formerly only a very low level of mitochondrial dysfunction gradually increases. And we already know that this growing dysfunction is accompanied by the onset of metabolic syndrome, neurodegenerative disorders, cardiomyopathy, and cancer. More recently, it has been scientifically proven that declines in autophagy (the process in which cells break down and recycle substances such as their old proteins and organelles using lysosomes) and decline in the level of nicotinamide adenine dinucleotide (NAD+<\/sup>) in the blood are also related to aging.<\/p>\n Allow me to provide a simple explanation of autophagy. When a cell is in a state of starvation, a vesicle called a phagophore, or isolation membrane, appears in the cytoplasm. This membrane envelops unnecessary substances in the cell. Once sealed, it is called an autophagosome. Autophagosomes contain mitochondria and other organelles. The autophagosomes then fuse with lysosomes, which break down their contents. We are conducting research into the degradation mechanism involved in autophagy, with a particular focus on the lysosomes with which autophagosomes fuse.<\/p>\n As NAD+<\/sup> activates energy production within the body, it is believed that it has a diverse array of effects, such as improving cellular function, delaying aging, enhancing cognitive function and exercise capacity, maintaining skin elasticity and luster, and boosting immune function. Reduced autophagy function and NAD+<\/sup> levels are known to be causes of age-related diseases. This coenzyme has been attracting increasing attention of late; in particular, research into the involvement of NAD+<\/sup> and sirtuin genes—a gene cluster that could potentially extend lifespan by curbing cellular aging—has been progressing, with research indicating that the view that NAD+<\/sup> supplementation is required to activate the sirtuin genes.<\/p>\n Which organs are affected by age-related mitochondrial dysfunction and in what way varies from one person to another. Accordingly, the organs subject to associated functional decline in the form of age-related diseases also differ according to the individual. We focused on the heart as an organ affected by aging. In order to investigate the relationship between reduced mitochondrial function in heart tissue and autophagy, particularly lysosomal function, we conducted an exhaustive analysis of cardiac tissue using a method called metabolomic analysis. As a result, we discovered that NAD+<\/sup> levels decrease. We are now moving forward with a study focused on why NAD+<\/sup> levels decrease and how we can prevent this decline.<\/p>\n Cardiomyocyte-specific p32 conditional knockout mice (p32cKO)—mice in which the molecule responsible for protein translation in mitochondria, the protein p32, had been removed—had a shorter lifespan than normal mice (which have a lifespan of around two years), at just one year when plotted on a survival curve (Figure 1). When we used ultrasound to check the cardiac function of these mice, we found that they had poor left ventricular ejection fraction and left ventricular fractional shortening. This means that cardiac systolic function was reduced, indicating a strong possibility of early-onset dilated cardiomyopathy. When we examined gene expression in heart failure markers (ANP and βMHC), and investigated cardiac fibrosis using Masson’s trichrome staining, we confirmed that the knockout mice did indeed have reduced cardiac function (Figures 2 and 3). We also found that mitochondrial translation was impaired in the cardiac tissue, leading to reduced protein expression. In other words, the loss of a single molecule that plays an important role in mitochondrial translation reduced cardiac function and shortened lifespan.<\/p>\n |
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Motoshi Hayano. Eijingu kakumei 250-sai made hito ga ikiru hi<\/i> [The Aging Revolution: The Day When People Will Live to Be 250]. p. 116–117, Asahi Shimbun Publications, 2024.<\/small><\/p>\n![\"\"](\"https:\/\/healthist.net\/en\/wp-content\/uploads\/sites\/3\/2026\/06\/297_en_feature01_02_fig02.png\")
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Modified from Asakawa S. in Nigiyaka na Tanbo: Inago ga Hane, Tori wa Mai, Sakana no Oyogu Shōuchū<\/i> [Paddy fields teeming with life: A microcosm where grasshoppers leap, birds flutter, and fish swim], ed. Natsuhara Y., p. 74, Information Design Associates Kyoto, 2015.<\/small><\/p>\n![\"\"](\"https:\/\/healthist.net\/en\/wp-content\/uploads\/sites\/3\/2026\/03\/296_en_feature01_02_fig01.jpg\")
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Yagi M. et al: Cardiovascular Research 2017:113 1173–85<\/small><\/p>\n