{"id":11746,"date":"2016-12-15T06:44:30","date_gmt":"2016-12-15T14:44:30","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&#038;p=11746"},"modified":"2024-01-30T15:37:23","modified_gmt":"2024-01-30T23:37:23","slug":"turning-back-time-salk-scientists-reverse-signs-aging","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/de\/news-release\/turning-back-time-salk-scientists-reverse-signs-aging\/","title":{"rendered":"Turning back time: Salk scientists reverse signs of aging"},"content":{"rendered":"<p>LA JOLLA\u2014Graying hair, crow\u2019s feet, an injury that\u2019s taking longer to heal than when we were 20\u2014faced with the unmistakable signs of aging, most of us have had a least one fantasy of turning back time. Now, scientists at the Salk Institute have found that intermittent expression of genes normally associated with an embryonic state can reverse the hallmarks of old age.<\/p>\n<div class=\"row\" style=\"\"><div class=\"col-md-10 col-md-push-1\"><div class=\"video-anchor\" id=\"video-3r_p__9EHxU\"><\/div><div class=\"embed-responsive embed-responsive-16by9\"> <iframe class=\"embed-responsive-item\" src=\"\/\/www.youtube.com\/embed\/3r_p__9EHxU?rel=0\" webkitallowfullscreen mozallowfullscreen allowfullscreen><\/iframe><\/div><!-- .embed-responsive --><\/div><!-- .col-md-*size --><\/div><!-- .\/row -->\n<p>This approach, which not only prompted human skin cells in a dish to look and behave young again, also resulted in the rejuvenation of mice with a premature aging disease, countering signs of aging and increasing the animals\u2019 lifespan by 30 percent. The early-stage work provides insight both into the cellular drivers of aging and possible therapeutic approaches for improving human health and longevity.<\/p>\n<p>\u201cOur study shows that aging may not have to proceed in one single direction,\u201d says <a href=\"https:\/\/www.salk.edu\/de\/scientist\/juan-carlos-izpisua-belmonte\/\">Juan Carlos Izpisua Belmonte<\/a>, a professor in Salk\u2019s Gene Expression Laboratory and senior author of the paper appearing in the December 15, 2016, issue of <a href=\"http:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(16)31664-6\" target=\"_blank\" rel=\"noopener\"><em>Zelle<\/em><\/a>. \u201cIt has plasticity and, with careful modulation, aging might be reversed.\u201d<\/p>\n<p>As people in modern societies live longer, their risk of developing age-related diseases goes up. In fact, data shows that the biggest risk factor for heart disease, cancer and neurodegenerative disorders is simply age. One clue to halting or reversing aging lies in the study of cellular reprogramming, a process in which the expression of four genes known as the Yamanaka factors allows scientists to convert any cell into induced pluripotent stem cells (iPSCs). Like embryonic stem calls, iPSCs are capable of dividing indefinitely and becoming any cell type present in our body.<\/p>\n<figure id=\"attachment_11780\"  class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"151\" class=\"img-responsive wp-image-11780 size-pr-300\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Cells-300x151.jpg\" alt=\"figure-cells\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Cells-300x151.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Cells-768x386.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Cells-1024x514.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Cells-147x74.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Cells-458x230.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Cells-585x294.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Cells-553x278.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Cells-750x377.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Cells-945x475.jpg 945w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><figcaption class=\"wp-caption-text\">Salk Institute researchers discover that partial cellular reprogramming reversed cellular signs of aging such as accumulation of DNA damage. (Left) Progeria mouse fibroblast cells; (right) progeria mouse fibroblast cells rejuvenated by partial reprogramming. <\/p>\n<p><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Cells.jpg\" target=\"_blank\" rel=\"noopener\">Klicken Sie hier<\/a> for a high-resolution image <\/p>\n<p>Kredit: Salk Institut<\/figcaption><\/figure>\n<p>\u201cWhat we and other stem-cell labs have observed is that when you induce cellular reprogramming, cells look younger,\u201d says Alejandro Ocampo, a research associate and first author of the paper. \u201cThe next question was whether we could induce this rejuvenation process in a live animal.\u201d<\/p>\n<p>While cellular rejuvenation certainly sounds desirable, a process that works for laboratory cells is not necessarily a good idea for an entire organism. For one thing, although rapid cell division is critical in growing embryos, in adults such growth is one of the hallmarks of cancer. For another, having large numbers of cells revert back to embryonic status in an adult could result in organ failure, ultimately leading to death. For these reasons, the Salk team wondered whether they could avoid cancer and improve aging characteristics by inducing the Yamanaka factors for a short period of time.<\/p>\n<p>To find out, the team turned to a rare genetic disease called progeria. Both mice and humans with progeria show many signs of aging including DNA damage, organ dysfunction and dramatically shortened lifespan. Moreover, the chemical marks on DNA responsible for the regulation of genes and protection of our genome, known as epigenetic marks, are prematurely dysregulated in progeria mice and humans. Importantly, epigenetic marks are modified during cellular reprogramming.<\/p>\n<figure id=\"attachment_11781\"  class=\"wp-caption alignleft\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"149\" class=\"img-responsive wp-image-11781 size-pr-300\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Muscle-300x149.jpg\" alt=\"figure-muscle\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Muscle-300x149.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Muscle-768x380.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Muscle-1024x507.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Muscle-147x73.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Muscle-458x227.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Muscle-585x290.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Muscle-553x274.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Muscle-750x371.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Muscle-945x468.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Muscle.jpg 1224w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><figcaption class=\"wp-caption-text\">Induction of reprogramming improved muscle regeneration in aged mice. (Left) impaired muscle repair in aged mice; (right) improved muscle regeneration in aged mice subjected to reprogramming. <\/p>\n<p><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Muscle.jpg\" target=\"_blank\" rel=\"noopener\">Klicken Sie hier<\/a> f\u00fcr ein hochaufl\u00f6sendes Bild.<\/p>\n<p>Kredit: Salk Institut<\/figcaption><\/figure>\n<p>Using skin cells from mice with progeria, the team induced the Yamanaka factors for a short duration. When they examined the cells using standard laboratory methods, the cells showed reversal of multiple aging hallmarks without losing their skin-cell identity.<\/p>\n<p>\u201cIn other studies scientists have completely reprogrammed cells all the way back to a stem-cell-like state,\u201d says co-first author Pradeep Reddy, also a Salk research associate. \u201cBut we show, for the first time, that by expressing these factors for a short duration you can maintain the cell\u2019s identity while reversing age-associated hallmarks.\u201d<\/p>\n<p>Encouraged by this result, the team used the same short reprogramming method during cyclic periods in live mice with progeria. The results were striking: Compared to untreated mice, the reprogrammed mice looked younger; their cardiovascular and other organ function improved and\u2014most surprising of all\u2014they lived 30 percent longer, yet did not develop cancer. On a cellular level, the animals showed the recovery of molecular aging hallmarks that are affected not only in progeria, but also in normal aging.<\/p>\n<p>\u201cThis work shows that epigenetic changes are at least partially driving aging,\u201d says co-first author Paloma Martinez-Redondo, another Salk research associate. \u201cIt gives us exciting insights into which pathways could be targeted to delay cellular aging.\u201d<\/p>\n<figure id=\"attachment_11782\"  class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"305\" class=\"img-responsive wp-image-11782 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/belmonte_IMG_6562e-458x305.jpg\" alt=\"belmonte_img_6562e\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/belmonte_IMG_6562e-458x305.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/belmonte_IMG_6562e-300x200.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/belmonte_IMG_6562e-768x512.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/belmonte_IMG_6562e-1024x683.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/belmonte_IMG_6562e-147x98.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/belmonte_IMG_6562e-585x390.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/belmonte_IMG_6562e-553x369.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/belmonte_IMG_6562e-750x500.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/belmonte_IMG_6562e-945x630.jpg 945w\" sizes=\"auto, (max-width: 458px) 100vw, 458px\" \/><figcaption class=\"wp-caption-text\">From left: Ergin Beyret, Mo Li, Aida Platero-Luengo, Pradeep Reddy, Paloma Martinez-Redondo, Eric Vazquez, Tomoaki Hishida, Toshikazu Araoka, Concepcion Rodriguez Esteban, Fumiyuki Hatanaka, Alejandro Ocampo, Juan Carlos Izpisua Belmonte<\/p>\n<p><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/belmonte_IMG_6562e.jpg\" target=\"_blank\" rel=\"noopener\">Klicken Sie hier<\/a> f\u00fcr ein hochaufl\u00f6sendes Bild. <\/p>\n<p>Kredit: Salk Institut<\/figcaption><\/figure>\n<p>Lastly, the Salk scientists turned their efforts to normal, aged mice. In these animals, the cyclic induction of the Yamanaka factors led to improvement in the regeneration capacity of pancreas and muscle. In this case, injured pancreas and muscle healed faster in aged mice that were reprogrammed, indicating a clear improvement in the quality of life by cellular reprogramming.<\/p>\n<p>\u201cObviously, mice are not humans and we know it will be much more complex to rejuvenate a person,\u201d says Izpisua Belmonte. \u201cBut this study shows that aging is a very dynamic and plastic process, and therefore will be more amenable to therapeutic interventions than what we previously thought.\u201d<\/p>\n<p>The Salk researchers believe that induction of epigenetic changes via chemicals or small molecules may be the most promising approach to achieve rejuvenation in humans. However, they caution that, due to the complexity of aging, these therapies may take up to 10 years to reach clinical trials.<\/p>\n<p>Other authors included: Aida Platero-Luengo, Fumiyuki Hatanaka, Tomoaki Hishida, Mo Li, David Lam, Masakazu Kurita, Ergin Beyret, Toshikazu Araoka, Eric Vazquez-Ferrer, David Donoso, Jose Luis Roman, Jinna Xu and Concepcion Rodriguez of the Salk Institute; Estrella Nu\u00f1ez Delicado of <a href=\"http:\/\/www.ucam.edu\/\" target=\"_blank\" rel=\"noopener\">Universidad Cat\u00f3lica San Antonio de Murcia<\/a>; Gabriel N\u00fa\u00f1ez of the <a href=\"https:\/\/medicine.umich.edu\/medschool\/\" target=\"_blank\" rel=\"noopener\">University of Michigan Medical School<\/a>; Josep Maria Campistol of <a href=\"http:\/\/www.hospitalclinic.org\/en\" target=\"_blank\" rel=\"noopener\">Hosplital Clinic of Barcelona<\/a> and Isabel Guill\u00e9n and Pedro Guill\u00e9n of <a href=\"http:\/\/www.fundacionpedroguillen.org\/el-dr-pedro-guillen\/\" target=\"_blank\" rel=\"noopener\">Fundaci\u00f3n Dr. Pedro Guill\u00e9n<\/a>.<\/p>\n<p>The work and the researchers involved were supported in part by a <a href=\"https:\/\/researchtraining.nih.gov\/programs\/training-grants\" target=\"_blank\" rel=\"noopener\">National Institutes of Health Ruth L. Kirschstein National Research Service Award Individual Postdoctoral Fellowship<\/a>, der <a href=\"https:\/\/www.mda.org\/\" target=\"_blank\" rel=\"noopener\">Muscular Dystrophy Association<\/a>, <a href=\"http:\/\/www.fundame.org\/en\/\" target=\"_blank\" rel=\"noopener\">Fundaci\u00f3n Alfonso Martin Escudero<\/a>, the Hewitt Foundation, the Uehara Memorial Foundation, the <a href=\"http:\/\/nomisfoundation.ch\/\" target=\"_blank\" rel=\"noopener\">Nomis Foundation<\/a>, a <a href=\"https:\/\/www.jsps.go.jp\/english\/e-ab\/\" target=\"_blank\" rel=\"noopener\">JSPS Postdoctoral Fellowship for Research Abroad<\/a>, der <a href=\"https:\/\/ucsd.edu\/\" target=\"_blank\" rel=\"noopener\">University of California, San Diego<\/a>, der <a href=\"http:\/\/www.mathersfoundation.org\/\" target=\"_blank\" rel=\"noopener\">G. Harold and Leila Y. Mathers Charitable Foundation<\/a>, <a href=\"http:\/\/www.helmsleytrust.org\/\" target=\"_blank\" rel=\"noopener\">Die Leona M. und Harry B. Helmsley Charitable Trust<\/a> (2012-PG-MED002), <a href=\"http:\/\/glennfoundation.org\/\" target=\"_blank\" rel=\"noopener\">The Glenn Foundation<\/a>, <a href=\"http:\/\/www.ucam.edu\/\" target=\"_blank\" rel=\"noopener\">Universidad Cat\u00f3lica San Antonio de Murcia (UCAM)<\/a> und <a href=\"http:\/\/www.fundacionpedroguillen.org\/el-dr-pedro-guillen\/\" target=\"_blank\" rel=\"noopener\">Fundaci\u00f3n Dr. Pedro Guill\u00e9n<\/a>.<\/p>","protected":false},"featured_media":11778,"template":"","faculty":[85],"disease-research":[146,335],"class_list":["post-11746","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-juan-carlos-izpisua-belmonte","disease-research-aging-and-regenerative-medicine","disease-research-regeneration"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Turning back time: Salk scientists reverse signs of 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\/de\/news-release\/turning-back-time-salk-scientists-reverse-signs-aging\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Turning back time: Salk scientists reverse signs of aging - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Graying hair, crow\u2019s feet, an injury that\u2019s taking longer to heal than when we were 20\u2014faced with the unmistakable signs of aging, most of us have had a least one fantasy of turning back time. Now, scientists at the Salk Institute have found that intermittent expression of genes normally associated with an embryonic state can reverse the hallmarks of old age.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.salk.edu\/de\/news-release\/turning-back-time-salk-scientists-reverse-signs-aging\/\" \/>\n<meta property=\"og:site_name\" content=\"Salk Institute for Biological Studies\" \/>\n<meta property=\"article:modified_time\" content=\"2024-01-30T23:37:23+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2016\/12\/Figure-Muscle-featured.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"475\" \/>\n\t<meta property=\"og:image:height\" content=\"475\" \/>\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=\"6 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\\\/turning-back-time-salk-scientists-reverse-signs-aging\\\/\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/turning-back-time-salk-scientists-reverse-signs-aging\\\/\",\"name\":\"Turning back time: Salk scientists reverse signs of aging - 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