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Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells

Tapash Jay Sarkar, Marco Quarta (), Shravani Mukherjee, Alex Colville, Patrick Paine, Linda Doan, Christopher M. Tran, Constance R. Chu, Steve Horvath, Lei S. Qi, Nidhi Bhutani, Thomas A. Rando and Vittorio Sebastiano ()
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Tapash Jay Sarkar: Stanford University School of Medicine
Marco Quarta: Stanford University School of Medicine
Shravani Mukherjee: Stanford University School of Medicine
Alex Colville: Stanford University School of Medicine
Patrick Paine: Stanford University School of Medicine
Linda Doan: Stanford University School of Medicine
Christopher M. Tran: Stanford University School of Medicine
Constance R. Chu: Stanford University School of Medicine
Steve Horvath: University of California
Lei S. Qi: Stanford University
Nidhi Bhutani: Stanford University School of Medicine
Thomas A. Rando: Stanford University School of Medicine
Vittorio Sebastiano: Stanford University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Aging is characterized by a gradual loss of function occurring at the molecular, cellular, tissue and organismal levels. At the chromatin level, aging associates with progressive accumulation of epigenetic errors that eventually lead to aberrant gene regulation, stem cell exhaustion, senescence, and deregulated cell/tissue homeostasis. Nuclear reprogramming to pluripotency can revert both the age and the identity of any cell to that of an embryonic cell. Recent evidence shows that transient reprogramming can ameliorate age-associated hallmarks and extend lifespan in progeroid mice. However, it is unknown how this form of rejuvenation would apply to naturally aged human cells. Here we show that transient expression of nuclear reprogramming factors, mediated by expression of mRNAs, promotes a rapid and broad amelioration of cellular aging, including resetting of epigenetic clock, reduction of the inflammatory profile in chondrocytes, and restoration of youthful regenerative response to aged, human muscle stem cells, in each case without abolishing cellular identity.

Date: 2020
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DOI: 10.1038/s41467-020-15174-3

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