{"id":597057,"date":"2023-01-13T05:49:26","date_gmt":"2023-01-13T11:49:26","guid":{"rendered":"https:\/\/news.sellorbuyhomefast.com\/index.php\/2023\/01\/13\/loss-of-epigenetic-information-can-drive-aging-in-mice\/"},"modified":"2023-01-13T05:49:26","modified_gmt":"2023-01-13T11:49:26","slug":"loss-of-epigenetic-information-can-drive-aging-in-mice","status":"publish","type":"post","link":"https:\/\/newsycanuse.com\/index.php\/2023\/01\/13\/loss-of-epigenetic-information-can-drive-aging-in-mice\/","title":{"rendered":"Loss of epigenetic information can drive aging in mice"},"content":{"rendered":"<div>\n                <main id=\"main\" role=\"main\" aria-label=\"Main content\"><br \/>\n                        <a id=\"main-content\"><\/a><\/p>\n<div>\n<section id=\"block-harvardmedical-content\">\n<article id=\"node-25651\" data-history-node-id=\"25651\" role=\"article\" about=\"\/news\/loss-epigenetic-information-can-drive-aging-restoration-can-reverse\">\n<div>\n<p><h2>Study in mice implicates changes to way DNA is organized, regulated rather than changes to genetic code itself<\/h2>\n<\/p><\/div>\n<div>\n<div>\n<p><span><br \/>\n        By STEPHANIE DUTCHEN<br \/>\n            <\/span><\/p>\n<p>                        <span><br \/>\n        <time datetime=\"2023-01-12T12:00:00Z\">January 12, 2023<\/time><\/p>\n<p>            <\/span><\/p>\n<p>                  <span><br \/>\n                      <a href=\"http:\/\/hms.harvard.edu\/news\/?f%5B0%5D=news_topic%3A206\" aria-label=\"Read other news articles about Research\">Research<\/a><br \/>\n                  <\/span><\/p>\n<p content=\"8\">\n        8 min read\n            <\/p>\n<\/p><\/div>\n<div>\n<section>\n<p>\n<iframe loading=\"lazy\" title=\"Embeded YouTube clip playing in a modal\" width=\"854\" height=\"480\" frameborder=\"0\" allowfullscreen=\"allowfullscreen\" src=\"https:\/\/player.vimeo.com\/video\/773472975?autoplay=0\"><\/iframe>\n<\/p>\n<p><img decoding=\"async\" loading=\"lazy\" src=\"http:\/\/hms.harvard.edu\/sites\/default\/files\/media\/mouse%20screen%20shot.png\" width=\"850\" height=\"430\" alt=\"Two mice sit on a ridged surface. One has darker hair and one is grayer\" typeof=\"foaf:Image\"><\/p>\n<p>\n            Genetics professor David Sinclair explains how changes to DNA organization and regulation can accelerate or reverse signs of aging in mice. Video: Rick Groleau and Bruce Walker\n          <\/p>\n<\/section>\n<div>\n<p><span><span><span><span><span><span><span>An international study 13 years in the making demonstrates for the first time that degradation in the way DNA is organized and regulated \u2014 known as epigenetics \u2014 can drive aging in an organism, independently of changes to the genetic code itself.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>The work shows that a breakdown in epigenetic information causes mice to age and that restoring the integrity of the epigenome reverses those signs of aging.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span><a href=\"https:\/\/hms.harvard.edu\/news-events\/sign-email-communications\">Get more HMS news here<\/a><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>Findings are <a href=\"https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(22)01570-7\"><span>published online Jan. 12 in <em>Cell<\/em><\/span><\/a><em>.<\/em><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>\u201cWe believe ours is the first study to show epigenetic change as a primary driver of aging in mammals,\u201d said the paper\u2019s senior author, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/17959\">David Sinclair<\/a>, professor of genetics in the Blavatnik Institute at Harvard Medical School and co-director of the <a href=\"https:\/\/www.hms.harvard.edu\/agingresearch\/\">Paul F. Glenn Center for Biology of Aging Research<\/a>.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>The team\u2019s extensive series of experiments provide long-awaited confirmation that DNA changes are not the only, or even the main, cause of aging. Rather, the findings show, chemical and structural changes to chromatin \u2014 the complex of DNA and proteins that forms chromosomes \u2014 fuel aging without altering the genetic code itself.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<\/p><\/div>\n<div>\n<div id=\"block-hmmemailpromosciencemedicinedelivered\">\n<h3>\n            Science &#038; Medicine, Delivered<br \/>\n          <\/h3>\n<p><em>Harvard Medicine<\/em>\u00a0magazine in your inbox<\/p>\n<\/p><\/div>\n<div>\n<p><span><span><span><span><span><span><span>\u201cWe expect the findings will transform the way we view the process of aging and the way we approach the treatment of diseases associated with aging,\u201d said co-first author <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/114266\">Jae-Hyun Yang<\/a>, research fellow in genetics in the Sinclair lab.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>The authors say that because it\u2019s easier to manipulate the molecules that control epigenetic processes than to reverse DNA mutations, the work points to new avenues that focus on epigenetics rather than genetics to prevent or treat age-related damage. <\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>First, the results need to be replicated in larger mammals and in humans. Studies in nonhuman primates are currently underway.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>\u201cWe hope these results are seen as a turning point in our ability to control aging,\u201d said Sinclair. \u201cThis is the first study showing that we can have precise control of the biological age of a complex animal; that we can drive it forwards and backwards at will.\u201d<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<h3><span><span><span><span><span><span><span><strong>Beyond mutations<\/strong><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/h3>\n<p><span><span><span><span><span><span><span>Perhaps the most burning question for those who study aging is what causes it.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>For decades, a reigning theory in the field was that aging arises from an accumulation of changes to DNA, primarily genetic mutations, which over time prevent more and more genes from functioning properly. These malfunctions, in turn, cause cells to lose their identity, so that tissues and organs break down, leading to disease and, ultimately, death.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>In recent years, however, studies have increasingly hinted that there\u2019s more to the story. <\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>For instance, some researchers found that some people and mice with high mutation rates don\u2019t show signs of premature aging. Others observed that many types of aged cells have few or no mutations.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>Researchers started wondering what else works with or instead of DNA changes to cause aging. A list of possible culprits grew. Among them were epigenetic changes.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>A component of epigenetics is the physical structures such as histones that bundle DNA into tightly compacted chromatin and unspool portions of that DNA when needed. Genes are inaccessible when they\u2019re bundled up but available to be copied and used to produce proteins when they\u2019re unspooled. Thus, epigenetic factors regulate which genes are active or inactive in any given cell at any given time.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>By acting as a toggle for gene activity, these epigenetic molecules help define cell type and function. Since each cell in an organism has basically the same DNA, it\u2019s the on-off switching of particular genes that differentiates a nerve cell from a muscle cell from a lung cell.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>\u201cEpigenetics is like a cell\u2019s operating system, telling it how to use the same genetic material differently,\u201d said Yang, who is co-first author with Motoshi Hayano, a former postdoctoral fellow in the Sinclair lab who is now at Keio University School of Medicine in Tokyo.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>In the late 1990s and early 2000s, Sinclair\u2019s lab and others showed in <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0092867400804936\">yeast<\/a> and <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2853975\/?report=reader\">mammals<\/a> that epigenetic changes accompany aging. Yet they couldn\u2019t tell whether these changes drove aging or were a consequence of it.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>It wasn\u2019t until the current study that Sinclair\u2019s team was able to disentangle epigenetic from genetic changes and confirm that a breakdown in epigenetic information does, in fact, contribute to aging in mice.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<h3><span><span><span><span><span><span><span><strong>ICE mice<\/strong><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/h3>\n<p><span><span><span><span><span><span><span>The team\u2019s main experiment involved creating temporary, fast-healing cuts in the DNA of lab mice. <\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>These breaks mimicked the low-grade, ongoing breaks in chromosomes that mammalian cells experience every day in response to things like breathing, exposure to sunlight and cosmic rays, and contact with certain chemicals.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>In the study, to test whether aging results from this process, the researchers sped the number of breaks to simulate life on fast-forward.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>The team also ensured that most of the breaks were not made within the coding regions of the mice\u2019s DNA \u2014 the segments that make up genes. This prevented the animals\u2019 genes from developing mutations. Instead, the breaks altered the way DNA is folded. <\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>Sinclair and colleagues called their system ICE, short for inducible changes to the epigenome.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>At first, epigenetic factors paused their normal job of regulating genes and moved to the DNA breaks to coordinate repairs. Afterward, the factors returned to their original locations.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>But as time passed, things changed. The researchers noticed that these factors got \u201cdistracted\u201d and did not return home after repairing breaks. The epigenome grew disorganized and began to lose its original information. Chromatin got condensed and unspooled in the wrong patterns, a hallmark of epigenetic malfunction.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>As the mice lost their youthful epigenetic function, they began to look and act old. The researchers saw a rise in biomarkers that indicate aging. Cells lost their identities as, for example, muscle or skin cells. Tissue function faltered. Organs failed.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>The team used <a href=\"https:\/\/hms.harvard.edu\/news\/clock\">a recent tool developed by Sinclair\u2019s lab<\/a> to measure how old the mice were, not chronologically, in days or months, but \u201cbiologically,\u201d based on how many sites across the genome lost the <a href=\"https:\/\/www.science.org\/doi\/full\/10.1126\/science.abn4009?et_rid=35378765\">methyl groups<\/a> normally attached to them. Compared to untreated mice born at the same time, the ICE mice had aged significantly more.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<h3><span><span><span><span><span><span><span><strong>Young again<\/strong><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/h3>\n<p><span><span><span><span><span><span><span>Next, the researchers gave the mice a gene therapy that reversed the epigenetic changes they\u2019d caused.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>\u201cIt\u2019s like rebooting a malfunctioning computer,\u201d said Sinclair. <\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>The therapy delivered a trio of genes \u2014 <em>Oct4<\/em>, <em>Sox2,<\/em> and <em>Klf4<\/em>, together named OSK \u2014 that are active in stem cells and can help rewind mature cells to an earlier state. (Sinclair\u2019s lab <a href=\"https:\/\/hms.harvard.edu\/news\/vision-revision\">used this cocktail to restore sight in blind mice<\/a>\u00a0in 2020.)<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>The ICE mice\u2019s organs and tissues resumed a youthful state.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>The therapy \u201cset in motion an epigenetic program that led cells to restore the epigenetic information they had when they were young,\u201d said Sinclair. \u201cIt\u2019s a permanent reset.\u201d<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>How exactly OSK treatment achieved that remains unclear.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>At this stage, Sinclair says the discovery supports the hypothesis that mammalian cells maintain a kind of backup copy of epigenetic software that, when accessed, can allow an aged, epigenetically scrambled cell to reboot into a youthful, healthy state.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>For now, the extensive experiments led the team to conclude that \u201cby manipulating the epigenome, aging can be driven forwards and backwards,\u201d said Yang.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<h3><span><span><span><span><span><span><span><strong>From here<\/strong><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/h3>\n<p><span><span><span><span><span><span><span>The ICE method offers researchers a new way to explore the role of epigenetics in aging and other biological processes. <\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>Because signs of aging developed in the ICE mice after only six months rather than toward the end of the average mouse life span of two and a half years, the approach also saves time and money for researchers studying aging.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>Researchers can also look beyond OSK gene therapy in exploring how lost epigenetic information might be restored in aged organisms.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>\u201cThere are other ways to manipulate the epigenome, like drugs and small molecule chemicals that induce gentle stress,\u201d said Yang. \u201cThis work opens a door for applying those other methods to rejuvenate cells and tissues.\u201d<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>Sinclair hopes the work inspires other scientists to study how to control aging to prevent and eliminate age-related diseases and conditions in humans, such as cardiovascular disease, type 2 diabetes, neurodegeneration, and frailty. <\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>\u201cThese are all manifestations of aging that we\u2019ve been trying to treat with medicines when they arise, which is almost too late,\u201d he said.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>The goal would be to address the root causes of aging to extend human health span: the number of years that a person remains not just alive but well. <\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>Medical applications are a long way off and will take extensive experiments in multiple cell and animal models. But, Sinclair said, scientists should think big and keep trying in order to achieve such dreams.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>\u201cWe\u2019re talking about taking someone who\u2019s old or sick and making their whole body or a specific organ young again, so the disease goes away,\u201d he said. \u201cIt\u2019s a big idea. It\u2019s not how we typically do medicine.\u201d<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<\/p><\/div>\n<div>\n<ul data-accordion data-multi-expand=\"true\" data-allow-all-closed=\"true\">\n<li data-accordion-item>\n<p>  <a href=\"http:\/\/hms.harvard.edu\/#\"><\/p>\n<div>\n<p><img decoding=\"async\" loading=\"lazy\" src=\"http:\/\/hms.harvard.edu\/sites\/default\/files\/styles\/accordion_image_230x200\/public\/2023-01\/Jae-Hyun_Yang.jpg?itok=A_Slt7Nc\" width=\"500\" height=\"450\" alt=\"Head shot of a young Korean man in glasses with bangs swept to one side\" typeof=\"foaf:Image\"><\/p>\n<div>\n<h3>            Long time coming<br \/>\n      <\/h3>\n<p><span>            <\/p>\n<p>The study marks the culmination of 10 years of Yang\u2019s career as a postdoctoral researcher. <\/p>\n<p>But there were moments along the way when he thought he\u2019d never see the work completed.<\/p>\n<p>      <\/span>\n              <\/p>\n<\/div><\/div>\n<p>  <\/a><\/p>\n<div data-tab-content>\n<p><span><span><span><span><span><span><span>As the scope expanded year after year, with colleagues and critics urging Yang to add more experiments and incorporate new technologies, the project often felt overwhelming. Yang sometimes listened to those who asked whether it was all worth it. At one point he drafted an email to Sinclair saying he wanted to quit the project.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>\u201cLuckily,\u201d said Sinclair, \u201che didn\u2019t send it.\u201d<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>The problem wasn\u2019t Yang\u2019s skills or dedication. Rather, the work was the most ambitious ever attempted in the lab. Sinclair thinks it may represent one of the hardest projects undertaken in science in recent years.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>\u201cYou don\u2019t get many chances in life to do a project like this,\u201d he said. \u201cIt took an incredible amount of mental and physical labor to get to this point. Jae and the team demonstrated so much resilience as we got rejected and re-reviewed and did six more years of experiments until we ended up with a body of work that answers one of the most important questions in biology. I\u2019m really proud of the team.\u201d<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>Seeing the findings published at long last not only offers professional satisfaction but also feels poignant on a personal level, Sinclair said.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>\u201cThis project began when I was 39. I\u2019m now 53,\u201d he said. \u201cA lot has happened in those years. We\u2019re older. Our families and friends have changed. People on the project have died. It\u2019s more than just a paper for us; it\u2019s a major part of our lives.\u201d<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>\u201cThere\u2019s a lot of emotion in this,\u201d he continued. \u201cI feel like some of my soul is in there.\u201d<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>For his part, Yang hopes to now become a principal investigator in Korea, where he grew up.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>\u201cI\u2019m very happy to have answered one of the long-standing questions in the field,\u201d he said. \u201cI\u2019m really looking forward to seeing the impact.\u201d\u00a0<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<\/p><\/div>\n<\/li>\n<\/ul><\/div>\n<div>\n<h3><span><span><span><span><span><span><span><strong>Authorship, funding, disclosures<\/strong><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/h3>\n<p><span><span><span><span><span><span><span>Additional authors on the study are <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/160919\">Patrick Griffin<\/a>, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/157737\">Jo\u00e3o Amorim<\/a>, Michael Bonkowski, John Apostolides, Elias Salfati, Marco Blanchette, Elizabeth Munding, Mital Bhakta, Yap Ching Chew, Wei Guo, Xiaojing Yang, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/198483\">Sun Maybury-Lewis<\/a>, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/171999\">Xiao Tian<\/a>, Jaime Ross, Giuseppe Coppotelli, Margarita Meer, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/202328\">Ryan Rogers-Hammond<\/a>, Daniel Vera, Yuancheng Lu, Jeffrey Pippin, Michael Creswell, Zhixun Dou, Caiyue Xu, Sarah Mitchell, Abhirup Das, Brendan O\u2019Connell, Sachin Thakur, Alice Kane, Qiao Su, Yasuaki Mohri, Emi Nishimura, Laura Schaevitz, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/192566\">Neha Garg<\/a>, Ana-Maria Balta, Meghan Rego, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/88346\">Meredith Gregory-Ksander<\/a>, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/23558\">Tatjana Jakobs<\/a>, Lei Zhong, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/57550\">Hiroko Wakimoto<\/a>, Jihad Andari, Dirk Grimm, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/78884\">Raul Mostoslavsky<\/a>, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/1943\">Amy Wagers<\/a>, Kazuo Tsubota, Stephen Bonasera, Carlos Palmeira, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/profile\/1256727\">Jonathan Seidman<\/a>, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/profile\/1251232\">Christine Seidman<\/a>, Norman Wolf, Jill Kreiling, John Sedivy, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/69208\">George Murphy<\/a>, Richard Green, Benjamin Garcia, Shelley Berger, Philipp Oberdoerffer, Stuart Shankland, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/4185\">Vadim Gladyshev<\/a>, <a href=\"https:\/\/connects.catalyst.harvard.edu\/Profiles\/display\/Person\/66254\">Bruce Ksander<\/a>, Andreas Pfenning, and <a href=\"https:\/\/sinclair.hms.harvard.edu\/people\/luis-rajman\">Luis Rajman<\/a>.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>This work was supported by the National Institutes of Health (grants R01AG019719, R37AG028730, R01EY019703, R01DK056799-10, R01DK056799-12, R01DK097598-01A1, T32AG023480, and K99AG055683), Glenn Foundation for Medical Research, Glenn\/AFAR Research Grants for Junior Faculty, National Research Foundation of Korea (2012R1A6A3A03040476), Human Frontier Science Program (LT000680\/2014-L), JSPS KAKENHI (17K13228, 19K16619 and 19H05269), Uehara Memorial Foundation, and St. Vincent de Paul Foundation. The authors also acknowledge the Dalio Foundation, Susan and Duane Hoff, the VoLo Foundation, and Edward Schulak.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>Sinclair is a consultant to, inventor of patents licensed to, and in some cases board member and investor of MetroBiotech, Cohbar, InsideTracker, Zymo, EdenRoc Sciences and affiliates including Cantata\/Dovetail, Life Biosciences and affiliates, Segterra, and Galilei Biosciences, Immetas, Animal Biosciences, and Tally Health. He is also an inventor on patent applications licensed to Bayer Crops, Merck KGaA, and Elysium Health. <a href=\"https:\/\/sinclair.hms.harvard.edu\/david-sinclairs-affiliations\">Details available here<\/a>. Munding, Blanchette, and Bhakta are employees of Dovetail Genomics. Chew, Guo, and Yang are employees of Zymo Research Corporation. Wagers is a consultant to Frequency Therapeutics and a co-founder of Elevian. Schaevitz was an employee of Vium. Lu and Rajman are equity owners of Life Biosciences. Vera and Bonkowski were advisors to Liberty Biosecurity. All other authors declare no competing interests.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<p><span><span><span><span><span><span><span>The authors dedicated their publication to the memory of co-authors Bonkowski and Wolf and supporter Paul F. Glenn.<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/p>\n<\/p><\/div>\n<\/p><\/div>\n<\/p><\/div>\n<\/p><\/div>\n<\/section>\n<section id=\"block-views-block-related-news-block-1\">\n<h2>Related News<\/h2>\n<\/section>\n<section id=\"block-views-block-hms-news-trending-block-2\">\n<h2>Trending News<\/h2>\n<\/section><\/div>\n<p>          <\/main><\/p><\/div>\n<p><a href=\"https:\/\/hms.harvard.edu\/news\/loss-epigenetic-information-can-drive-aging-restoration-can-reverse\" class=\"button purchase\" rel=\"nofollow noopener\" target=\"_blank\">Read More<\/a><br \/>\n Anthony Fetzer<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Study in mice implicates changes to way DNA is organized, regulated rather than changes to genetic code itself By STEPHANIE DUTCHEN January 12, 2023 Research 8 min read Genetics professor David Sinclair explains how changes to DNA organization and regulation can accelerate or reverse signs of aging in mice. Video: Rick Groleau and Bruce Walker<\/p>\n","protected":false},"author":1,"featured_media":597058,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[51921,4751,46],"tags":[],"class_list":{"0":"post-597057","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-epigenetic","8":"category-information","9":"category-technology"},"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/posts\/597057","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/comments?post=597057"}],"version-history":[{"count":0,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/posts\/597057\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/media\/597058"}],"wp:attachment":[{"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/media?parent=597057"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/categories?post=597057"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/newsycanuse.com\/index.php\/wp-json\/wp\/v2\/tags?post=597057"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}