Chemically induced reprogramming to reverse cellular aging
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Published version
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2.08 MB
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Author(s)
Yang, Jae-Hyun
Petty, Christopher A
Dixon-McDougall, Thomas
Lopez, Maria Vina
Tyshkovskiy, Alexander
Maybury-Lewis, Sun
Tian, Xiao
Ibrahim, Nabilah
Chen, Zhili
Griffin, Patrick T
Date Issued
July 12, 2023
Journal
Aging
Publisher
Impact Journals, LLC
Citation
Yang J, Petty CA, Dixon-McDougall T, Lopez MV, Tyshkovskiy A, Maybury-Lewis S, Tian X, Ibrahim N, Chen Z, Griffin PT, Arnold M, Li J, Martinez OA, et al. Chemically induced reprogramming to reverse cellular aging. Aging (Albany NY). 2023 Jul 12; 15:5966-5989.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.18632/aging.204896
