{"id":2536,"date":"2015-04-30T00:00:00","date_gmt":"2015-04-30T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/scientists-discover-key-driver-of-human-aging\/"},"modified":"2016-02-07T09:09:34","modified_gmt":"2016-02-07T17:09:34","slug":"scientists-discover-key-driver-of-human-aging","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/scientists-discover-key-driver-of-human-aging\/","title":{"rendered":"Scientists discover key driver of human aging"},"content":{"rendered":"<p>\nLA JOLLA\u2013A study tying the aging process to the deterioration of tightly packaged bundles of cellular DNA could lead to methods of preventing and treating age-related diseases such as cancer, diabetes and Alzheimer\u2019s disease, as detailed April 30, 2015, in <em><a href=\"http:\/\/www.sciencemag.org\/content\/early\/2015\/04\/29\/science.aaa1356.abstract\" target=\"_blank\">\u79d1\u5b66<\/a><\/em>.\n<\/p>\n<p>\nIn the study, scientists at the Salk Institute and the <a href=\"http:\/\/english.cas.cn\/\" target=\"_blank\">Chinese Academy of Science<\/a> found that the genetic mutations underlying Werner syndrome, a disorder that leads to premature aging and death, resulted in the deterioration of bundles of DNA known as heterochromatin.\n<\/p>\n<p><iframe src=\"\/\/www.youtube.com\/embed\/oMZICp0OWww\" frameborder=\"0\" allowfullscreen><\/iframe><\/p>\n<p>\nThe discovery, made possible through a combination of cutting-edge stem cell and gene-editing technologies, could lead to ways of countering age-related physiological declines by preventing or reversing damage to heterochromatin.\n<\/p>\n<p>\n\u201cOur findings show that the gene mutation that causes Werner syndrome results in the disorganization of heterochromatin, and that this disruption of normal DNA packaging is a key driver of aging,\u201d says <a href=\"https:\/\/www.salk.edu\/zh\/faculty\/belmonte.html\/\" target=\"_blank\">Juan Carlos Izpisua Belmonte<\/a>, a senior author on the paper. \u201cThis has implications beyond Werner syndrome, as it identifies a central mechanism of aging\u2013heterochromatin disorganization\u2013which has been shown to be reversible.\u201d\n<\/p>\n<p>\nWerner syndrome is a genetic disorder that causes people to age more rapidly than normal. It affects around one in every 200,000 people in the United States. People with the disorder suffer age-related diseases early in life, including cataracts, type 2 diabetes, hardening of the arteries, osteoporosis and cancer, and most die in their late 40s or early 50s.\n<\/p>\n<div class=\"imageCaption\"><img decoding=\"async\" style=\"border-bottom: 1px #006699 solid;\" alt=\"\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/01\/2080-BelmonteAgingImage.jpg\"><\/p>\n<p>Salk Institute researchers discovered that a protein mutated in the premature aging disorder, Werner syndrome, plays a key role in stabilizing heterochromatin, a tightly packaged form of DNA. More generally, the findings suggest that heterochromatin disorganization may be a key driver of aging. This image shows normal human cells (left) and genetically modified cells developed by the Salk scientists to model Werner syndrome (right), which showed signs of aging, including their large size.  <\/p>\n<p><a target=\"_blank\" href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/02\/2080-BelmonteAgingImage.jpg\">Click here<\/a> for a high-resolution image.<\/p>\n<p>\nImage: Courtesy of the Salk Institute for Biological Studies\n<\/p>\n<\/div>\n<p>\nThe disease is caused by a mutation to the Werner syndrome RecQ helicase-like gene, known as the WRN gene for short, which generates the WRN protein. Previous studies showed that the normal form of the protein is an enzyme that maintains the structure and integrity of a person\u2019s DNA. When the protein is mutated in Werner syndrome it disrupts the replication and repair of DNA and the expression of genes, which was thought to cause premature aging. However, it was unclear exactly how the mutated WRN protein disrupted these critical cellular processes.\n<\/p>\n<p>\nIn their study, the Salk scientists sought to determine precisely how the mutated WRN protein causes so much cellular mayhem. To do this, they created a cellular model of Werner syndrome by using a cutting-edge gene-editing technology to delete WRN gene in human stem cells. This stem cell model of the disease gave the scientists the unprecedented ability to study rapidly aging cells in the laboratory. The resulting cells mimicked the genetic mutation seen in actual Werner syndrome patients, so the cells began to age more rapidly than normal. On closer examination, the scientists found that the deletion of the WRN gene also led to disruptions to the structure of heterochromatin, the tightly packed DNA found in a cell\u2019s nucleus.\n<\/p>\n<p>\nThis bundling of DNA acts as a switchboard for controlling genes\u2019 activity and directs a cell\u2019s complex molecular machinery. On the outside of the heterochromatin bundles are chemical markers, known as epigenetic tags, which control the structure of the heterochromatin. For instance, alterations to these chemical switches can change the architecture of the heterochromatin, causing genes to be expressed or silenced.\n<\/p>\n<figure  class=\"wp-caption alignright\"><img decoding=\"async\" alt=\"From left: Pradeep Reddy, Concepcion Rodriguez Esteban, Emi Suzuki, Mo Li, Juan Carlos Izpisua Belmonte, Alejandro Ocampo, Keiichiro Suzuki\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/01\/2080-Pradeep-Reddy_Concepcion-Rodriguez-Esteban_Emi-Suzuki_Mo-Li_Juan-Carlos-Izpisua-Belmonte_Alejandro-Ocampo_Keiichiro-Suzuki_IMG_9887e-530.jpg\"><figcaption class=\"wp-caption-text\"><\/p>\n<p>\nFrom left: Pradeep Reddy, Concepcion Rodriguez Esteban, Emi Suzuki, Mo Li, Juan Carlos Izpisua Belmonte, Alejandro Ocampo, Keiichiro Suzuki<\/p>\n<p><a target=\"_blank\" href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/02\/2080-Pradeep-Reddy_Concepcion-Rodriguez-Esteban_Emi-Suzuki_Mo-Li_Juan-Carlos-Izpisua-Belmonte_Alejandro-Ocampo_Keiichiro-Suzuki_IMG_9887e.jpg\">Click here<\/a> for a high-resolution image.<\/p>\n<p>\nImage: Courtesy of the Salk Institute for Biological Studies\n<\/p>\n<p><\/figcaption><\/figure>\n<p>\nThe Salk researchers discovered that deletion of the WRN gene leads to heterochromatin disorganization, pointing to an important role for the WRN protein in maintaining heterochromatin. And, indeed, in further experiments, they showed that the protein interacts directly with molecular structures known to stabilize heterochromatin\u2013revealing a kind of smoking gun that, for the first time, directly links mutated WRN protein to heterochromatin destabilization.\n<\/p>\n<p>\n\u201cOur study connects the dots between Werner syndrome and heterochromatin disorganization, outlining a molecular mechanism by which a genetic mutation leads to a general disruption of cellular processes by disrupting epigenetic regulation,\u201d says Izpisua Belmonte. \u201cMore broadly, it suggests that accumulated alterations in the structure of heterochromatin may be a major underlying cause of cellular aging. This begs the question of whether we can reverse these alterations\u2013like remodeling an old house or car\u2013to prevent, or even reverse, age-related declines and diseases.\u201d\n<\/p>\n<p>\nIzpisua Belmonte added that more extensive studies will be needed to fully understand the role of heterochromatin disorganization in aging, including how it interacts with other cellular processes implicated in aging, such as shortening of the end of chromosomes, known as telomeres. In addition, the Izpisua Belmonte team is developing epigenetic editing technologies to reverse epigenetic alterations with a role in human aging and disease.\n<\/p>\n<p>\nOther authors on the paper include: Weiqi Zhang, Jingyi Li, Keiichiro Suzuki, Jing Qu, Ping Wang, Junzhi Zhou, Xiaomeng Liu, Ruotong Ren, Xiuling Xu, Alejandro Ocampo, Tingting Yuan, Jiping Yang, Ying Li, Liang Shi, Dee Guan, Huize Pan, Shunlei Duan, Zhichao Ding, Mo Li, Fei Yi, Ruijun Bai, Yayu Wang, Chang Chen, Fuquan Yang, Xiaoyu Li, Zimei Wang, Emi Aizawa, April Goebl, Rupa Devi Soligalla, Pradeep Reddy, Concepcion Rodriguez Esteban, Fuchou Tang and Guang-Hui Liu.\n<\/p>\n<p>\nFunding for the study was provided by the <a href=\"http:\/\/glennfoundation.org\/\" target=\"_blank\">Glenn Foundation<\/a>, the <a href=\"http:\/\/www.mathersfoundation.org\/\" target=\"_blank\">G. Harold and Leila Y. Mathers Charitable Foundation<\/a> and the <a href=\"http:\/\/helmsleytrust.org\/\" target=\"_blank\">Leona M. and Harry B. Helmsley Charitable Trust<\/a>.\n<\/p>\n<p>\n<strong>About the Salk Institute for Biological Studies:<\/strong><br \/>\nThe Salk Institute for Biological Studies is one of the world&#8217;s preeminent basic research institutions, where internationally renowned faculty probes fundamental life science questions in a unique, collaborative and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer&#8217;s, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology and related disciplines.\n<\/p>\n<p>\nFaculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, MD, the Institute is an independent nonprofit organization and architectural landmark.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[85],"disease-research":[127,165,146,162],"class_list":["post-2536","disclosure","type-disclosure","status-publish","hentry","faculty-juan-carlos-izpisua-belmonte","disease-research-alzheimers-disease","disease-research-diabetes-type-2","disease-research-aging-and-regenerative-medicine","disease-research-parkinsons-disease"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Scientists discover key driver of human aging - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/scientists-discover-key-driver-of-human-aging\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Scientists discover key driver of human aging - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2013A study tying the aging process to the deterioration of tightly packaged bundles of cellular DNA could lead to methods of preventing and treating age-related diseases such as cancer, diabetes and Alzheimer\u2019s disease, as detailed April 30, 2015, in Science.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.salk.edu\/zh\/news-release\/scientists-discover-key-driver-of-human-aging\/\" \/>\n<meta property=\"og:site_name\" content=\"Salk Institute for Biological Studies\" \/>\n<meta property=\"article:modified_time\" content=\"2016-02-07T17:09:34+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk-institute-preview-image.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"628\" \/>\n\t<meta property=\"og:image:height\" content=\"329\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"5 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/scientists-discover-key-driver-of-human-aging\\\/\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/scientists-discover-key-driver-of-human-aging\\\/\",\"name\":\"Scientists discover key driver of human aging - Salk Institute for Biological Studies\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/scientists-discover-key-driver-of-human-aging\\\/#primaryimage\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/scientists-discover-key-driver-of-human-aging\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2015\\\/01\\\/2080-BelmonteAgingImage.jpg\",\"datePublished\":\"2015-04-30T07:00:00+00:00\",\"dateModified\":\"2016-02-07T17:09:34+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/scientists-discover-key-driver-of-human-aging\\\/#breadcrumb\"},\"inLanguage\":\"zh-CN\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/scientists-discover-key-driver-of-human-aging\\\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"zh-CN\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/scientists-discover-key-driver-of-human-aging\\\/#primaryimage\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2015\\\/01\\\/2080-BelmonteAgingImage.jpg\",\"contentUrl\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2015\\\/01\\\/2080-BelmonteAgingImage.jpg\"},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/scientists-discover-key-driver-of-human-aging\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/www.salk.edu\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Scientists discover key driver of human aging\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"name\":\"Salk Institute for Biological Studies\",\"description\":\"The Power of Science\",\"publisher\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/www.salk.edu\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"zh-CN\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\",\"name\":\"Salk Institute for Biological Studies\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"zh-CN\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"contentUrl\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"width\":696,\"height\":696,\"caption\":\"Salk Institute for Biological Studies\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Scientists discover key driver of human aging - Salk Institute for Biological Studies","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.salk.edu\/zh\/news-release\/scientists-discover-key-driver-of-human-aging\/","og_locale":"zh_CN","og_type":"article","og_title":"Scientists discover key driver of human aging - Salk Institute for Biological Studies","og_description":"LA JOLLA\u2013A study tying the aging process to the deterioration of tightly packaged bundles of cellular DNA could lead to methods of preventing and treating age-related diseases such as cancer, diabetes and Alzheimer\u2019s disease, as detailed April 30, 2015, in Science.","og_url":"https:\/\/www.salk.edu\/zh\/news-release\/scientists-discover-key-driver-of-human-aging\/","og_site_name":"Salk Institute for Biological Studies","article_modified_time":"2016-02-07T17:09:34+00:00","og_image":[{"width":628,"height":329,"url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk-institute-preview-image.jpg","type":"image\/jpeg"}],"twitter_card":"summary_large_image","twitter_misc":{"Est. reading time":"5 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/www.salk.edu\/news-release\/scientists-discover-key-driver-of-human-aging\/","url":"https:\/\/www.salk.edu\/news-release\/scientists-discover-key-driver-of-human-aging\/","name":"Scientists discover key driver of human aging - Salk Institute for Biological Studies","isPartOf":{"@id":"https:\/\/www.salk.edu\/#website"},"primaryImageOfPage":{"@id":"https:\/\/www.salk.edu\/news-release\/scientists-discover-key-driver-of-human-aging\/#primaryimage"},"image":{"@id":"https:\/\/www.salk.edu\/news-release\/scientists-discover-key-driver-of-human-aging\/#primaryimage"},"thumbnailUrl":"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/01\/2080-BelmonteAgingImage.jpg","datePublished":"2015-04-30T07:00:00+00:00","dateModified":"2016-02-07T17:09:34+00:00","breadcrumb":{"@id":"https:\/\/www.salk.edu\/news-release\/scientists-discover-key-driver-of-human-aging\/#breadcrumb"},"inLanguage":"zh-CN","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.salk.edu\/news-release\/scientists-discover-key-driver-of-human-aging\/"]}]},{"@type":"ImageObject","inLanguage":"zh-CN","@id":"https:\/\/www.salk.edu\/news-release\/scientists-discover-key-driver-of-human-aging\/#primaryimage","url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/01\/2080-BelmonteAgingImage.jpg","contentUrl":"https:\/\/www.salk.edu\/wp-content\/uploads\/2015\/01\/2080-BelmonteAgingImage.jpg"},{"@type":"BreadcrumbList","@id":"https:\/\/www.salk.edu\/news-release\/scientists-discover-key-driver-of-human-aging\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.salk.edu\/"},{"@type":"ListItem","position":2,"name":"Scientists discover key driver of human aging"}]},{"@type":"WebSite","@id":"https:\/\/www.salk.edu\/#website","url":"https:\/\/www.salk.edu\/","name":"\u7d22\u5c14\u514b\u751f\u7269\u7814\u7a76\u6240","description":"The Power of Science","publisher":{"@id":"https:\/\/www.salk.edu\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.salk.edu\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"zh-CN"},{"@type":"Organization","@id":"https:\/\/www.salk.edu\/#organization","name":"\u7d22\u5c14\u514b\u751f\u7269\u7814\u7a76\u6240","url":"https:\/\/www.salk.edu\/","logo":{"@type":"ImageObject","inLanguage":"zh-CN","@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/","url":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","contentUrl":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","width":696,"height":696,"caption":"Salk Institute for Biological Studies"},"image":{"@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/"}}]}},"ACF":{"paper_url":"http:\/\/www.sciencemag.org\/content\/early\/2015\/04\/29\/science.aaa1356.abstract","journal_title":"Science","paper_author_list":"Weiqi Zhang, Jingyi Li, Keiichiro Suzuki, Jing Qu, Ping Wang, Junzhi Zhou, Xiaomeng Liu, Ruotong Ren, Xiuling Xu, Alejandro Ocampo, Tingting Yuan, Jiping Yang, Ying Li, Liang Shi, Dee Guan, Huize Pan, Shunlei Duan, Zhichao Ding, Mo Li, Fei Yi, Ruijun Bai, Yayu Wang, Chang Chen, Fuquan Yang, Xiaoyu Li, Zimei Wang, Emi Aizawa, April Goebl, Rupa Devi Soligalla, Pradeep Reddy, Concepcion Rodriguez Esteban, Fuchou Tang, Guang-Hui Liu, Juan Carlos Izpisua Belmonte","paper_title":"A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging","subhead":"Salk Institute findings on premature aging syndrome could lead to way  of slowing or reversing aging process","home_photo":"2080.jpg","listing_photo":"2080-BelmonteAgingImage.jpg","gallery":false,"legacy_boilerplate":[]},"_links":{"self":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure\/2536","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure"}],"about":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/types\/disclosure"}],"version-history":[{"count":0,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disclosure\/2536\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/media?parent=2536"}],"wp:term":[{"taxonomy":"faculty","embeddable":true,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/faculty?post=2536"},{"taxonomy":"disease-research","embeddable":true,"href":"https:\/\/www.salk.edu\/zh\/wp-json\/wp\/v2\/disease-research?post=2536"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}