Chemically Induced Reprogramming to Reverse Cellular Aging | Aging-US

Aging-US published this Priority Research Paper on July 12, 2023, entitled, “Chemically induced reprogramming to reverse cellular aging" by researchers from the Paul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA; Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119234, Russia; Molecular and Biomedical Sciences, University of Maine, Orono, ME; Department of Biology and Chemistry, Massachusetts Institute of Technology, Cambridge, MA. ‪@harvardmedicalschool‬
#aging #reprogramming #epigenetics #rejuvenation #medicine #molecules #research #researchpaper #openaccess #openscience #peerreview #journal #publication #publishing #meded

DOI - https://doi.org/10.18632/aging.204896

Corresponding author - David A. Sinclair - [email protected]

Press release - https://www.aging-us.com/news_room/NE...

Abstract

A hallmark of eukaryotic aging is a loss of epigenetic information, a process that can be reversed. We have previously shown that the ectopic induction of the Yamanaka factors OCT4, SOX2, and KLF4 (OSK) in mammals can restore youthful DNA methylation patterns, transcript profiles, and tissue function, without erasing cellular identity, a process that requires active DNA demethylation. To screen for molecules that reverse cellular aging and rejuvenate human cells without altering the genome, we developed high-throughput cell-based assays that distinguish young from old and senescent cells, including transcription-based aging clocks and a real-time nucleocytoplasmic compartmentalization (NCC) assay. We identify six chemical cocktails, which, in less than a week and without compromising cellular identity, restore a youthful genome-wide transcript profile and reverse transcriptomic age. Thus, rejuvenation by age reversal can be achieved, not only by genetic, but also chemical means.

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Keywords - aging, reprogramming, rejuvenation medicine, information theory of aging, small molecules, epigenetics

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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