Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function.
Document Type
Article
Publication Date
8-6-2024
Original Citation
Wang B,
Wang L,
Gasek N,
Kuo C,
Nie J,
Kim T,
Yan P,
Zhu J,
Torrance B,
Zhou Y,
Flores L,
Allen C,
Andrade A,
Guo C,
Cohn R,
Jellison E,
Bartley J,
Kuchel G,
Li S,
Pirtskhalava T,
Tchkonia T,
Yadav S,
Haynes L,
Kirkland J,
Ikeno Y,
Xu M.
Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function. Cell Metab. 2024;36(8):1795-805.e6.
Keywords
Animals, Cyclin-Dependent Kinase Inhibitor p21, Longevity, Mice, Mice, Inbred C57BL, Male, Aging, Female
JAX Source
Cell Metab. 2024;36(8):1795-805.e6.
ISSN
1932-7420
PMID
39111286
DOI
https://doi.org/10.1016/j.cmet.2024.07.006
Abstract
A key challenge in aging research is extending lifespan in tandem with slowing down functional decline so that life with good health (healthspan) can be extended. Here, we show that monthly clearance, starting from 20 months, of a small number of cells that highly express p21Cip1 (p21high ) improves cardiac and meta- bolic function and extends both median and maximum lifespans in mice. Importantly, by assessing the 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 healthspan extension. Mechanistically, p21high cells encompass several cell types with a relatively conserved proinflammatory signature. Clearance of p21high cells reduces inflammation and alleviates age-related transcriptomic signatures of various tissues. These findings demonstrate the feasibility of healthspan extension in mice and indicate p21high cells as a ther- apeutic target for healthy aging.