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

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...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications Vol. 11; no. 1; pp. 1545 - 12
Main Authors: Sarkar, Tapash Jay, Quarta, Marco, Mukherjee, Shravani, Colville, Alex, Paine, Patrick, Doan, Linda, Tran, Christopher M., Chu, Constance R., Horvath, Steve, Qi, Lei S., Bhutani, Nidhi, Rando, Thomas A., Sebastiano, Vittorio
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 24.03.2020
Nature Publishing Group
Nature Portfolio
Subjects:
13
13/100
13/106
14
14/1
38
38/79
49
49/91
631/443/7
631/532/2435
631/61/2320
631/80
Adolescent
Adult
Age
Aged
Aged, 80 and over
Aging
Aging - physiology
Animals
Cell Nucleus - metabolism
Cells, Cultured
Cellular Reprogramming - physiology
Cellular Senescence - physiology
Chondrocytes
Chromatin
Deregulation
DNA Methylation - physiology
Embryos
Endothelial Cells
Epigenesis, Genetic - physiology
Epigenetics
Exhaustion
Female
Fibroblasts
Gene expression
Gene Expression Profiling
Gene regulation
Homeostasis
Humanities and Social Sciences
Humans
Inflammation
Intravital Microscopy
Life span
Male
Mice
Middle Aged
multidisciplinary
Muscle Cells
Muscles
Pluripotency
Primary Cell Culture
Rejuvenation - physiology
Restoration
RNA, Messenger - metabolism
Science
Science (multidisciplinary)
Senescence
Stem cell transplantation
Stem Cells
Young Adult
ISSN:2041-1723, 2041-1723
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Aging involves gradual loss of tissue function, and transcription factor (TF) expression can ameliorate this in progeroid mice. Here the authors show that transient TF expression reverses age-associated epigenetic marks, inflammatory profiles and restores regenerative potential in naturally aged human cells.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-15174-3