2026-02-26 ロックフェラー大学
＜関連情報＞
- https://www.rockefeller.edu/news/39031-scientists-map-how-aging-reshapes-cells-across-the-entire-mammalian-body/
- https://www.science.org/doi/10.1126/science.adw6273
哺乳類の老化における生物全体の細胞動態とエピゲノムリモデリング Organism-wide cellular dynamics and epigenomic remodeling in mammalian aging
Ziyu Lu, Zehao Zhang, Zihan Xu, Abdulraouf Abdulraouf, […] , and Junyue Cao
Science Published:26 Feb 2026
Editor’s summary
Aging atlases have been generated for multiple organisms, but they are often restricted to capturing the transcriptional landscape across cells. Lu et al. created a single-cell chromatin accessibility atlas in mice for 21 tissues over three age time points (see the Perspective by Barnett and Noseda). They combined this atlas with a previous gene expression atlas of aging and found many changes in cellular composition and chromatin accessibility with aging. Changes occurred across cell types, but immune cells in particular showed diverging patterns with aging, and the authors were able to trace these patterns to particular transcription factor motifs within the peaks. Many of these changes were sex specific, reinforcing the importance of using diverse samples in such endeavors. —Corinne Simonti
Structured Abstract
INTRODUCTION
Aging is the leading risk factor for many diseases. This association underscores the potential of therapies targeting the aging process itself to delay or prevent age-related diseases. Substantial advances in single-cell genomics have enabled the profiling of alterations in aging. However, these analyses typically focus on transcriptomics and overlook the impact of chromatin landscapes.
RATIONALE
Single-cell assay for transposase-accessible chromatin using sequencing (ATAC-seq), which analyzes genome-wide chromatin accessibility at the single-cell level, has enabled the mapping of the cell type–specific chromatin landscape in a range of mammalian tissues. With a further optimized version of single-cell ATAC-seq by combinatorial indexing (EasySci-ATAC), we investigated aging-associated changes in cell populations and chromatin changes across the entire organism, aiming to identify aging-associated noncoding regions and their corresponding cell types.
RESULTS
In this study, we applied EasySci-ATAC to profile chromatin accessibility in more than 10 million nuclei across 21 tissue types from mice spanning three age groups (1 month, 5 months, and 21 months). We detected a total of 1.3 million cis-regulatory elements and identified cell type–specific usages of them. We reported aging-associated population dynamics of 536 tissue-level main cell types and 1828 finer-grained subtypes. In broadly distributed cell types, we observed coordinated expansion or depletion of the same subtype in multiple organs. At the molecular level, we identified extensive chromatin reprogramming with aging, including changes in the accessibility of individual peaks and certain transcription factor motifs, and linked them to expression changes of putative target genes. Moreover, we detected extensive sexual dimorphism, including age-conserved, sex-specific chromatin states for the same cell types and age-sex interaction effects at both proportional and molecular levels.
CONCLUSION
Our organism-level single-cell chromatin accessibility atlas illuminates how aging remodels cellular composition and regulatory regions of multiple tissues. In addition to many highly tissue-specific changes, we uncovered coordinated cellular and molecular dynamics that are shared across different organs, including immune remodeling, broad depletion of functional cell types, the emergence of inflammation-related states, and sex-dependent trajectories. By cataloging these changes, we offer a resource for understanding the molecular logic of aging and for guiding therapeutic strategies aimed at preserving or restoring youthful tissue states. Looking forward, we anticipate that this atlas will serve as a critical reference for evaluating anti-aging interventions and refining our understanding of how chromatin remodeling, cell state transitions, and tissue physiology intersect in the aging mammalian body. We have created an interactive website to facilitate exploration of these freely available data: https://epiage.net/.
An organism-wide single-cell atlas of chromatin accessibility reveals cellular dynamics and epigenomic remodeling during aging.
We applied EasySci-ATAC-seq to profile chromatin accessibility in more than 10 million cells across 21 mouse tissues, spanning three age groups and both sexes. This comprehensive dataset enables the identification of age-associated shifts in cell populations, shared aging dynamics across broadly distributed cell types, and chromatin landscape reprogramming during aging, as well as age-sex interacting changes. [Mouse illustration created with BioRender.com]
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.
