Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-15174-3
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Funding
- AFAR Junior Investigator Award
- National Institutes of Health (NIH/NIAMS) [R01 AR070865, R01 AR070864]
- Glenn Foundation for Medical Research
- National Institutes of Health (NIH) [P01 AG036695, R01 AG23806, R01 AG057433, R01 AG047820]
- Department of Veterans Affairs (BLRD Merit Review)
- Department of Veterans Affairs (RRD Merit Review)
- CalPoly funding Award [TB1-01175]
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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.
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