SIRT3 deficiency decreases oxidative metabolism capacity but increases lifespan in male mice under caloric restriction
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.
From the paper
- Events by group
Both Sirt3 −/− groups performed poorly, displaying critical velocity for Sirt3 −/− CD and Sirt3 −/− CR mice that were 24% and 27% slower than that of their diet matched control animals.
Results, Loss of SIRT3 limits aerobic fitness due to reduced mitochondrial respiration capacity
Quoted word for word from the full text on PubMed Central.
The paper
University of Wisconsin–Madison
Aging Cell, 5 Oct 2022, Open access
