SIRT3 deficiency exacerbates cognitive decline by disrupting mitochondrial antioxidant homeostasis in D-galactose-induced aging mice.

ABSTRACT:

Background

Age-related cognitive decline poses a growing clinical burden, with mitochondrial oxidative stress recognized as a key mediator. Sirtuin 3 (SIRT3), a mitochondrial deacetylase, is a potential regulator of redox balance, but its role in hippocampal function and cognitive aging, particularly its translational potential, remains unclear.

Methods

We used D-galactose (D-gal)-treated mice (150 mg/kg/day for 8 weeks) to model accelerated aging and neuron-specific SIRT3 knockout (SIRT3^cKO) mice. Transcriptomic profiling, behavioral tests, electrophysiological recordings, and mitochondrial analyses were performed. Therapeutic potential was assessed via intrahippocampal AAV-SIRT3 overexpression.

Results

D-gal induced memory deficits, disrupted hippocampal

SUBMITTER: An X 

PROVIDER: S-EPMC12802234 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature