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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Published in:	BioEssays Vol. 45; no. 4; pp. e2200208 - n/a
Main Authors:	Puri, Deepika, Wagner, Wolfgang
Format:	Journal Article
Language:	English
Published:	United States Wiley Subscription Services, Inc 01.04.2023
Subjects:	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
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Abstract	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.
AbstractList	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. 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. 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.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.
Author	Puri, Deepika Wagner, Wolfgang
Author_xml	– sequence: 1 givenname: Deepika surname: Puri fullname: Puri, Deepika email: dpuri@ukaachen.de organization: RWTH Aachen University Medical School – sequence: 2 givenname: Wolfgang orcidid: 0000-0002-1971-3217 surname: Wagner fullname: Wagner, Wolfgang email: wwagner@ukaachen.de organization: RWTH Aachen University Medical School
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Snippet	Rejuvenation of cells by reprogramming toward the pluripotent state raises increasing attention. In fact, generation of induced pluripotent stem cells (iPSCs)...
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SubjectTerms	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
Title	Epigenetic rejuvenation by partial reprogramming
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