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Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells.
- Source :
-
Nature communications [Nat Commun] 2020 Mar 24; Vol. 11 (1), pp. 1545. Date of Electronic Publication: 2020 Mar 24. - Publication Year :
- 2020
-
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.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Aging physiology
Animals
Cells, Cultured
Chondrocytes
DNA Methylation physiology
Endothelial Cells
Epigenesis, Genetic physiology
Female
Fibroblasts
Gene Expression Profiling
Humans
Intravital Microscopy
Male
Mice
Middle Aged
Muscle Cells
Primary Cell Culture
Stem Cells
Young Adult
Cell Nucleus metabolism
Cellular Reprogramming physiology
Cellular Senescence physiology
RNA, Messenger metabolism
Rejuvenation physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 32210226
- Full Text :
- https://doi.org/10.1038/s41467-020-15174-3