SIRT1 is downregulated by autophagy in senescence and ageing.

ABSTRACT: SIRT1 (Sir2) is an NAD⁺-dependent deacetylase that plays critical roles in a broad range of biological events, including metabolism, the immune response and ageing^1-5. Although there is strong interest in stimulating SIRT1 catalytic activity, the homeostasis of SIRT1 at the protein level is poorly understood. Here we report that macroautophagy (hereafter referred to as autophagy), a catabolic membrane trafficking pathway that degrades cellular components through autophagosomes and lysosomes, mediates the downregulation of mammalian SIRT1 protein during senescence and in vivo ageing. In senescence, nuclear SIRT1 is recognized as an autophagy substrate and is subjected to cytoplasmic autophagosome-lysosome degradation, via the autophagy protein LC3. Importantly, the aut

SUBMITTER: Xu C 

PROVIDER: S-EPMC7805578 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature