Organism-wide cellular dynamics and epigenomic remodeling in mammalian aging.

Publication Type Academic Article
Authors Lu Z, Zhang Z, Xu Z, Abdulraouf A, Zhou W, Cao J
Journal Science
Volume 391
Issue 6788
Pagination eadw6273
Date Published 02/26/2026
ISSN 1095-9203
Abstract To investigate organism-wide cellular alterations and epigenomic dynamics during aging, we constructed a single-cell chromatin accessibility atlas spanning 21 mouse tissues across three age groups and both sexes. We found that around one-quarter of 536 organ-specific cell types and 1828 finer-grained subtypes exhibited considerable age-related population shifts. Cellular states from broadly distributed lineages displayed synchronized dynamics with age, indicating systemic signals that coordinate these changes. Molecular analyses identified both intrinsic regulators (chromatin peaks, transcription factor activity) and extrinsic factors (cytokine programs) underlying these shifts. Moreover, ~40% of aging-associated population dynamics were sex-dependent, with tens of thousands of peaks altered exclusively in one sex. Together, these findings present a comprehensive framework for how aging reshapes the chromatin landscape and cellular composition across diverse tissues.
DOI 10.1126/science.adw6273
PubMed ID 41747035
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