Epigenetic rejuvenation by partial reprogramming

Rejuvenation of cells by reprogramming toward the pluripotent state raises increasing attention. In fact, generation of induced pluripotent stem cells (iPSCs) completely reverses age‐associated molecular features, including elongation of telomeres, resetting of epigenetic clocks and age‐associated t...

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Veröffentlicht in:BioEssays Jg. 45; H. 4; S. e2200208 - n/a
Hauptverfasser: Puri, Deepika, Wagner, Wolfgang
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Wiley Subscription Services, Inc 01.04.2023
Schlagworte:
ageing clock
Aging
Cell Differentiation
Cell fate
cell senescence
Cellular Reprogramming - genetics
Clocks
DNA methylation
Elongation
Epigenesis, Genetic
epigenetic
Epigenetics
Induced Pluripotent Stem Cells
interrupted reprogramming
iPSC
partial reprogramming
Pluripotency
pluripotent
Rejuvenation
reprogramming
risk
Senescence
Stem cells
Telomeres
Teratoma
Transcriptomics
transient reprogramming
pluripotent
reprogramming
ageing clock
transient reprogramming
epigenetic
iPSC
DNA methylation
interrupted reprogramming
rejuvenation
partial reprogramming
ISSN:0265-9247, 1521-1878, 1521-1878
Online-Zugang:Volltext
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Zusammenfassung:Rejuvenation of cells by reprogramming toward the pluripotent state raises increasing attention. In fact, generation of induced pluripotent stem cells (iPSCs) completely reverses age‐associated molecular features, including elongation of telomeres, resetting of epigenetic clocks and age‐associated transcriptomic changes, and even evasion of replicative senescence. However, reprogramming into iPSCs also entails complete de‐differentiation with loss of cellular identity, as well as the risk of teratoma formation in anti‐ageing treatment paradigms. Recent studies indicate that partial reprogramming by limited exposure to reprogramming factors can reset epigenetic ageing clocks while maintaining cellular identity. So far, there is no commonly accepted definition of partial reprogramming, which is alternatively called interrupted reprogramming, and it remains to be elucidated how the process can be controlled and if it resembles a stable intermediate state. In this review, we discuss if the rejuvenation program can be uncoupled from the pluripotency program or if ageing and cell fate determination are inextricably linked. Alternative rejuvenation approaches with reprogramming into a pluripotent state, partial reprogramming, transdifferentiation, and the possibility of selective resetting of cellular clocks are also discussed. Generation of induced pluripotent stem cells (iPSCs) completely reverses age‐associated molecular features, but it also entails loss of cellular identity. Partial reprogramming can reset epigenetic ageing clocks while maintaining cellular identity. We discuss if the rejuvenation program can be uncoupled from the pluripotency program or if ageing and cell fate determination are inextricably linked.
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ISSN:0265-9247
1521-1878
1521-1878
DOI:10.1002/bies.202200208