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

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

Nature communications (2020-03-27)
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, Vittorio Sebastiano
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-HP1γ Antibody, clone 42s2, clone 42s2, Upstate®, from mouse
Sigma-Aldrich
Anti-Luciferase antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Collagen from calf skin, Bornstein and Traub Type I, (0.1% solution in 0.1 M acetic acid), aseptically processed, BioReagent, suitable for cell culture
Millipore
Millicell® EZ Slide, 8-well glass chamber slide, 0.7 cm2/well, 96/pk, sterile