Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming.
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Authors
Chondronasiou, Dafni
Durand, Sylvere
Aprahamian, Fanny
Nirmalathasan, Nitharsshini
Kroemer, Guido
Publication Date
2022-03Journal Title
Aging Cell
ISSN
1474-9718
Publisher
Wiley
Volume
21
Issue
3
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Chondronasiou, D., Gill, D., Mosteiro, L., Urdinguio, R. G., Berenguer-Llergo, A., Aguilera, M., Durand, S., et al. (2022). Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming.. Aging Cell, 21 (3) https://doi.org/10.1111/acel.13578
Abstract
The expression of the pluripotency factors OCT4, SOX2, KLF4, and MYC (OSKM) can convert somatic differentiated cells into pluripotent stem cells in a process known as reprogramming. Notably, partial and reversible reprogramming does not change cell identity but can reverse markers of aging in cells, improve the capacity of aged mice to repair tissue injuries, and extend longevity in progeroid mice. However, little is known about the mechanisms involved. Here, we have studied changes in the DNA methylome, transcriptome, and metabolome in naturally aged mice subject to a single period of transient OSKM expression. We found that this is sufficient to reverse DNA methylation changes that occur upon aging in the pancreas, liver, spleen, and blood. Similarly, we observed reversion of transcriptional changes, especially regarding biological processes known to change during aging. Finally, some serum metabolites and biomarkers altered with aging were also restored to young levels upon transient reprogramming. These observations indicate that a single period of OSKM expression can drive epigenetic, transcriptomic, and metabolomic changes toward a younger configuration in multiple tissues and in the serum.
Keywords
Aging, Pluripotency, Reprogramming, Oskm, Yamanaka, Epigenetic Clocks, Transcriptomic Clocks
Sponsorship
Fundación Científica Asociación Española Contra el Cáncer (PROYE18061FERN)
European Research Council (ERC‐2014‐AdG/669622, ERC-2014-AdG/669622)
Ministerio de Ciencia e Innovación (SAF2013-48256-R, SAF2013‐48256‐R)
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0425)
Identifiers
35235716, PMC8920440
External DOI: https://doi.org/10.1111/acel.13578
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335717
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