Oxidative stress impairs the Nur77-Sirt1 axis resulting in a decline in organism homeostasis during aging.

ABSTRACT: Sirt1 is an NAD⁺ -dependent deacetylase that protects against premature aging and cell senescence. Aging accompanied by oxidative stress leads to a decrease in Sirt1 levels and activity, but the regulatory mechanism that connects these events remains unclear. Here, we reported that Nur77, which shares similar biological pathways with Sirt1, was also decreased with age in multiple organs. Our in vivo and in vitro results revealed that Nur77 and Sirt1 decreased during aging and oxidative stress-induced cell senescence. Deletion of Nr4a1 shortened the lifespan and accelerated the aging process in multiple mouse tissues. Overexpression of Nr4a1 protected the Sirt1 protein from proteasomal degradation through negative transcriptional regulation of the E3 ligase MDM2. Our results show

SUBMITTER: Yu Y 

PROVIDER: S-EPMC10186606 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature