SIRT2 counteracts primate cardiac aging via deacetylation of STAT3 that silences CDKN2B.
Nat Aging
; 3(10): 1269-1287, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37783815
ABSTRACT
Aging is a major risk factor contributing to pathophysiological changes in the heart, yet its intrinsic mechanisms have been largely unexplored in primates. In this study, we investigated the hypertrophic and senescence phenotypes in the hearts of aged cynomolgus monkeys as well as the transcriptomic and proteomic landscapes of young and aged primate hearts. SIRT2 was identified as a key protein decreased in aged monkey hearts, and engineered SIRT2 deficiency in human pluripotent stem cell-derived cardiomyocytes recapitulated key senescence features of primate heart aging. Further investigations revealed that loss of SIRT2 in human cardiomyocytes led to the hyperacetylation of STAT3, which transcriptionally activated CDKN2B and, in turn, triggered cardiomyocyte degeneration. Intra-myocardial injection of lentiviruses expressing SIRT2 ameliorated age-related cardiac dysfunction in mice. Taken together, our study provides valuable resources for decoding primate cardiac aging and identifies the SIRT2-STAT3-CDKN2B regulatory axis as a potential therapeutic target against human cardiac aging and aging-related cardiovascular diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteômica
/
Sirtuína 2
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
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Animals
/
Humans
Idioma:
En
Revista:
Nat Aging
Ano de publicação:
2023
Tipo de documento:
Article