Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function.
Cell Metab
; 36(8): 1795-1805.e6, 2024 Aug 06.
Article
en En
| MEDLINE
| ID: mdl-39111286
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 metabolic 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 therapeutic target for healthy aging.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Inhibidor p21 de las Quinasas Dependientes de la Ciclina
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Longevidad
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Ratones Endogámicos C57BL
Límite:
Animals
Idioma:
En
Revista:
Cell Metab
/
Cell metab
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Cell metabolism
Asunto de la revista:
METABOLISMO
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos