Intermittent Clearance of p21-Highly-Expressing Cells Extends Lifespan and Confers Sustained Benefits to Health and Physical Function

Authors

• Binsheng Wang
• Lichao Wang
• Nathan S Gasek
• Chia-Ling Kuo
• Jia Nie
• Taewan Kim
• Pengyi Yan
• Junyu Zhu
• Blake L Torrance
• Yueying Zhou
• Lisa C Flores
• Colton Allen
• Allison M Andrade
• Chun Guo
• Rachel L Cohn
• Evan R Jellison
• Jenna M Bartley
• George A Kuchel
• Sheng Li
• Tamar Pirtskhalava
• Tamar Tchkonia
• Sumit Yadav
• Laura Haynes
• James L Kirkland
• Yuji Ikeno
• Ming Xu

Language

English

Publication Date

8-6-2024

Journal

Cell Metabolism

DOI

10.1016/j.cmet.2024.07.006

PMID

39111286

PMCID

PMC11315361

PubMedCentral® Posted Date

8-6-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

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 monthly 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 healthspan extension. Mechanistically, p21high cells encompass several cell types, with a relatively conserved pro-inflammatory 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 therapeutic target for healthy aging.

Keywords

Animals, Cyclin-Dependent Kinase Inhibitor p21, Longevity, Mice, Mice, Inbred C57BL, Male, Aging, Female, cellular senescence, morbidity compression, inflammation, frailty, aging

Published Open-Access

yes

Recommended Citation

Wang, Binsheng; Wang, Lichao; Gasek, Nathan S; et al., "Intermittent Clearance of p21-Highly-Expressing Cells Extends Lifespan and Confers Sustained Benefits to Health and Physical Function" (2024). Faculty, Staff and Student Publications. 4309.
https://digitalcommons.library.tmc.edu/uthmed_docs/4309