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Repeated intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function

GSE269660 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2024/06/13 Platform GPL24247
Summary
A key challenge in aging research is to extend lifespan in tandem with slowing down functional decline so that the life with good health (healthspan) can be extended. Here, we show that clearance of a small number of cells, which highly express p21Cip1 (p21high), starting from 20 months improves cardiac and metabolic function, and extends both median and maximum lifespan in mice. Importantly, by assessing health and physical function of these mice monthly until death, we show that clearance of p21high cells improves physical function at all remaining stages of life, suggesting morbidity compression and healthspan extension. Mechanistically, p21high cells encompass several cell types, with a conserved pro-inflammatory signature. Clearance of p21high cells reduces inflammation, and rejuvenates transcriptomic signatures of various tissues to younger states. These findings demonstrate the feasibility of morbidity compression in mice, and indicate p21high cells as a therapeutic target for healthy aging.
Published in
Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function
Wang B, Wang L, Gasek NS et al. · Cell metabolism 2024 · PMID 39111286 · doi:10.1016/j.cmet.2024.07.006
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Also filed as BioProject PRJNA1123176 and SRA study SRP513426. Searching any of these in the dataset finder brings you back here.

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