Apoptosis signal-regulating kinase 1 promotes inflammation in senescence and aging.
Commun Biol
; 7(1): 691, 2024 Jun 05.
Article
en En
| MEDLINE
| ID: mdl-38839869
ABSTRACT
Cellular senescence is a stress-induced, permanent cell cycle arrest involved in tumor suppression and aging. Senescent cells secrete bioactive molecules such as pro-inflammatory cytokines and chemokines. This senescence-associated secretory phenotype (SASP) has been implicated in immune-mediated elimination of senescent cells and age-associated chronic inflammation. However, the mechanisms regulating the SASP are incompletely understood. Here, we show that the stress-responsive kinase apoptosis signal-regulating kinase 1 (ASK1) promotes inflammation in senescence and aging. ASK1 is activated during senescence and increases the expression of pro-inflammatory cytokines and chemokines by activating p38, a kinase critical for the SASP. ASK1-deficient mice show impaired elimination of oncogene-induced senescent cells and an increased rate of tumorigenesis. Furthermore, ASK1 deficiency prevents age-associated p38 activation and inflammation and attenuates glomerulosclerosis. Our results suggest that ASK1 is a driver of the SASP and age-associated chronic inflammation and represents a potential therapeutic target for age-related diseases.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Envejecimiento
/
Senescencia Celular
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MAP Quinasa Quinasa Quinasa 5
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Inflamación
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Commun Biol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón