SIRT3 deficiency decreases oxidative metabolism capacity but increases lifespan in male mice under caloric restriction.
Aging Cell
; 21(12): e13721, 2022 Dec.
Article
em En
| MEDLINE
| ID: mdl-36199173
ABSTRACT
Mitochondrial NAD+ -dependent protein deacetylase Sirtuin3 (SIRT3) has been proposed to mediate calorie restriction (CR)-dependent metabolic regulation and lifespan extension. Here, we investigated the role of SIRT3 in CR-mediated longevity, mitochondrial function, and aerobic fitness. We report that SIRT3 is required for whole-body aerobic capacity but is dispensable for CR-dependent lifespan extension. Under CR, loss of SIRT3 (Sirt3-/- ) yielded a longer overall and maximum lifespan as compared to Sirt3+/+ mice. This unexpected lifespan extension was associated with altered mitochondrial protein acetylation in oxidative metabolic pathways, reduced mitochondrial respiration, and reduced aerobic exercise capacity. Also, Sirt3-/- CR mice exhibit lower spontaneous activity and a trend favoring fatty acid oxidation during the postprandial period. This study shows the uncoupling of lifespan and healthspan parameters (aerobic fitness and spontaneous activity) and provides new insights into SIRT3 function in CR adaptation, fuel utilization, and aging.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Restrição Calórica
/
Sirtuína 3
/
Longevidade
Limite:
Animals
Idioma:
En
Revista:
Aging Cell
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos