{"id":2082,"date":"2011-02-23T00:00:00","date_gmt":"2011-02-23T08:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/aging-interrupted\/"},"modified":"2022-06-17T08:33:05","modified_gmt":"2022-06-17T15:33:05","slug":"aging-interrupted","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/de\/news-release\/aging-interrupted\/","title":{"rendered":"Aging, interrupted"},"content":{"rendered":"<p>LA JOLLA, CA\u2014The current pace of population aging is without parallel in human history but surprisingly little is known about the human aging process, because lifespans of eight decades or more make it difficult to study. Now, researchers at the Salk Institute for Biological Studies replicated premature aging in the lab, allowing them to study ageing-related disease in a dish.<\/p>\n<p>In the February 23, 2011 advance online edition of the journal <em>Natur<\/em>, <a href=\"\/de\/faculty\/belmonte.html\/\">Juan-Carlos Izpis\u00faa Belmonte<\/a>, Ph.D. a professor in the Salk Institute&#8217;s Gene Expression Laboratory, and his team report that they successfully generated induced pluripotent stem (iPS) cells from skin cells obtained from patients with Hutchinson-Gilford progeria-who age eight to 10 times faster than the rest of us-and differentiated them into smooth muscle cells displaying the telltale signs of vascular aging.<\/p>\n<p>&#8220;The slow progression and complexity of the aging process makes it very hard to study the pathogenesis of cardiovascular and other ageing-related disorders,&#8221; says Izpis\u00faa Belmonte. &#8220;Having a human model of accelerated aging may give us new insights into how we age. It may also help prevent or treat heart disease in the general aging population.<\/p>\n<div class=\"row\" style=\"\"><div class=\"col-md-12 col-md-push-0\"><div class=\"video-anchor\" id=\"video-PYwdntfxJCw\"><\/div><div class=\"embed-responsive embed-responsive-16by9\"> <iframe class=\"embed-responsive-item\" src=\"\/\/www.youtube.com\/embed\/PYwdntfxJCw?rel=0\" webkitallowfullscreen mozallowfullscreen allowfullscreen><\/iframe><\/div><!-- .embed-responsive --><\/div><!-- .col-md-*size --><\/div><!-- .\/row -->\n<p>Progeria&#8217;s striking features resemble the aging process put on fast-forward and afflicted people rarely live beyond 13 years. Almost all of the patients die from complications of arteriosclerosis-the clogging or hardening of arteries or blood vessels caused by plaques-which leads to heart attack and stroke.<\/p>\n<p>Scientists are particularly interested in progeria in the hopes that it might reveal clues to the normal human aging process. However, the disease is exceedingly rare and only 64 children living with progeria are known making access to patients very difficult.<\/p>\n<p>Hutchinson-Gilford progeria is caused by a single point mutation in the gene encoding lamin A, which forms a protein scaffold on the inner edge of the nucleus that helps maintain chromatin structure and organize nuclear processes such as RNA and DNA synthesis. The mutation creates an alternative splice site that leads to the production of a truncated version of the protein known as progerin. Unlike the full-length protein, progerin does not properly integrate into the nuclear lamina, which disrupts the nuclear scaffold and causes a host of problems.<\/p>\n<p>&#8220;There is also evidence that defective lamin A accumulates during the normal aging process via the sporadic use of the alternative splice site, &#8221; explains Izpis&amp;uactue;a Belmonte. &#8220;Therefore we are very keen on using our in vitro iPS cell-based model to identify new aging markers and explore other aspects of human premature and physiological aging.&#8221;<\/p>\n<p>Compared to normal skin fibroblasts, cells from progeria patients have misshapen nuclei and a range of other nuclear defects, including a disorganized nuclear lamina, loss of super-condensed DNA, telomere shortening and genomic instability. Yet, despite their &#8220;old&#8221; appearance and against all predictions, these cells could be readily converted into iPS cells.<\/p>\n<p>&#8220;The reprogramming process erased all nuclear and epigenetic defects and the rejuvenated pluripotent cells looked and acted like perfectly normal healthy cells,&#8221; says first author Guang-Hui Liu, Ph.D., a postdoctoral researcher in the Belmonte lab.<\/p>\n<p>Since lamin A is only expressed in differentiated cells but is absent from embryonic stem cells, he wondered whether iPS cells produce lamin A and\/or progerin, which should follow the same expression pattern as lamin A. In his experiments, he couldn&#8217;t detect either one. &#8220;The biological clock is reset in these cells because lamin A is silenced,&#8221; explains Liu.<\/p>\n<p>As soon as the Salk researchers differentiated progeria-derived iPS cells, progerin expression was reactivated. &#8220;This reversible suppression of progerin expression by reprogramming and subsequent reactivation during differentiation, provides a unique model system to study human premature ageing pathologies,&#8221; says Izpis\u00faa Belmonte.<\/p>\n<p>Progerin accumulates mainly in smooth muscle cells found within the walls of arterial blood vessels, and vascular smooth muscle cells degeneration is one of the hallmarks of Hutchinson-Gilford progeria syndrome-associated arteriosclerosis. In fact, vascular smooth muscle cell senescence also plays a role in advanced arteriosclerosis within the normal aging population.<\/p>\n<p>Upon directed differentiation of progeria-derived iPS cells into smooth muscle cells the premature aging phenotype, including misshapen nuclei, the loss of gene silencing marks and compromised proliferation, reappeared. Genetically modifying progeria-derived iPS cells to shut down the expression of progerin staved off the premature appearance of aging phenotypes after differentiation. &#8220;Transplantation of the progenitor cells derived from the &#8220;corrected&#8221; progeria iPS cells might hold the promise to treat these progeria children in the future.&#8221; says Liu.<\/p>\n<p>Other researchers contributing the study include Basam Z. Barkho, Sergio Ruiz, Jing Qu, Scheng-Liang Yang, Athanasia D. Panopoulos, Keiichiro Suzuki, Leo Kuraian, Christopher Walsh and Ignacio Sancho-Martinez in the Gene Expression Laboratory at the Salk Institute, Dinh Diep and Ho Lim Fung in the Department of Engineering at the University of California, San Diego, James Thompson and John Yates III in the Department of Cell Biology at the Scripps Research Institute and Stephanie Boue at the Center for Regenerative Medicine in Barcelona.<\/p>\n<p>For information on the commercialization of this technology, please contact Claudia Hetzer at 858-453-4100, x 1704 (<a href=\"mailto:chetzer@salk.edu\">chetzer@salk.edu<\/a>) in the Salk Office of Technology Management and Development.<\/p>\n<p>The study was supported by the California Institute of Regenerative Medicine, the AFAR\/Ellison Medical Foundation, the G. Harold and Leila Y. Mathers Charitable Foundation, Sanofi-Aventis, MICINN, the Fundacion Cellex and grants from the National Institutes of Health.<\/p>\n<p><strong><br \/>\n\u00dcber das Salk Institute for Biological Studies:<\/strong><\/p>\n<p>Das Salk Institute for Biological Studies ist eine der weltweit f\u00fchrenden Institutionen f\u00fcr Grundlagenforschung, an der international renommierte Fakult\u00e4tsmitglieder grundlegende Fragen der Biowissenschaften in einem einzigartigen, kollaborativen und kreativen Umfeld untersuchen. Mit dem Fokus auf Entdeckungen und die Ausbildung zuk\u00fcnftiger Forschergenerationen leisten Salk-Wissenschaftler bahnbrechende Beitr\u00e4ge zu unserem Verst\u00e4ndnis von Krebs, Alterung, Alzheimer, Diabetes und Infektionskrankheiten durch die Untersuchung von Neurowissenschaften, Genetik, Zell- und Pflanzenbiologie sowie verwandten Disziplinen.<\/p>\n<p>Die Leistungen der Fakult\u00e4t wurden mit zahlreichen Auszeichnungen gew\u00fcrdigt, darunter Nobelpreise und Mitgliedschaften in der National Academy of Sciences. Das 1960 vom Polio-Impfstoff-Pionier Dr. Jonas Salk gegr\u00fcndete Institut ist eine unabh\u00e4ngige gemeinn\u00fctzige Organisation und ein architektonisches Wahrzeichen.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[85],"disease-research":[],"class_list":["post-2082","disclosure","type-disclosure","status-publish","hentry","faculty-juan-carlos-izpisua-belmonte"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Aging, interrupted - 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\/aging-interrupted\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Aging, interrupted - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA, CA\u2014The current pace of population aging is without parallel in human history but surprisingly little is known about the human aging process, because lifespans of eight decades or more make it difficult to study. 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