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A hyper-quiescent chromatin state formed during aging is reversed by regeneration

Na Yang, James R. Occean, Daniël P. Melters, Changyou Shi, Lin Wang, Stephanie Stransky, Maı̀re E. Doyle, Chang‐Yi Cui, Michael Delannoy, Jinshui Fan, Eliza Slama, Josephine M. Egan, Supriyo De, Steven C. Cunningham, Rafael de Cabo

Molecular Cell · 2023 · ▲ 61 citations

Epigenetic alterations Mouse

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Abstract

Epigenetic alterations are a key hallmark of aging but have been limitedly explored in tissues. Here, using naturally aged murine liver as a model and extending to other quiescent tissues, we find that aging is driven by temporal chromatin alterations that promote a refractory cellular state and compromise cellular identity. Using an integrated multi-omics approach and the first direct visualization of aged chromatin, we find that globally, old cells show H3K27me3-driven broad heterochromatinization and transcriptional suppression. At the local level, site-specific loss of H3K27me3 over promoters of genes encoding developmental transcription factors leads to expression of otherwise non-hepatocyte markers. Interestingly, liver regeneration reverses H3K27me3 patterns and rejuvenates multiple molecular and physiological aspects of the aged liver.

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Provenance

Source: OpenAlex
DOI: 10.1016/j.molcel.2023.04.005
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Fetched: 2026-07-24 MST

Cite this

APA

Yang, N., Occean, J.R., Melters, D.P., Shi, C., Wang, L., Stransky, S., Doyle, M.E., Cui, C., Delannoy, M., Fan, J., Slama, E., Egan, J.M., De, S., Cunningham, S.C., Cabo, R.D., Sidoli, S., Dalal, Y., & Sen, P. (2023). A hyper-quiescent chromatin state formed during aging is reversed by regeneration. <em>Molecular Cell</em>. https://doi.org/10.1016/j.molcel.2023.04.005

Vancouver

Yang N, Occean JR, Melters DP, Shi C, Wang L, Stransky S, et al. A hyper-quiescent chromatin state formed during aging is reversed by regeneration. Molecular Cell. 2023. doi:10.1016/j.molcel.2023.04.005.

BibTeX

@article{na2023Ahyper, title = {A hyper-quiescent chromatin state formed during aging is reversed by regeneration}, author = {Na Yang and James R. Occean and Daniël P. Melters and Changyou Shi and Lin Wang and Stephanie Stransky and Maı̀re E. Doyle and Chang‐Yi Cui and Michael Delannoy and Jinshui Fan and Eliza Slama and Josephine M. Egan and Supriyo De and Steven C. Cunningham and Rafael de Cabo and Simone Sidoli and Yamini Dalal and Payel Sen}, journal = {Molecular Cell}, year = {2023}, doi = {10.1016/j.molcel.2023.04.005}, }