Reduced SIRT3 contributes to large elastic artery stiffness with aging

Abstract

Age‐related increases in arterial stiffness are mediated in part by mitochondrial dysfunction. Sirtuin 3 (SIRT3) is a mitochondrial NAD+‐dependent deacetylase that regulates mitochondrial function. SIRT3 deficiency contributes to physiological dysfunction in a variety of pathological conditions. Here, we tested the hypothesis that age‐associated arterial stiffness, assessed by aortic pulse wave velocity (aPWV), would be accompanied with decreased SIRT3 expression and activity. Old (~26 mo, n = 9) C57BL/6N male mice had higher aPWV vs. young (6 mo, n = 10) (448 ±14 vs 382 ± 13, p < 0.005), which was associated with reduced arterial and renal SIRT3 protein expression (0.17 ± 0.04 n=5 vs 0.57 ± 0.11 n=7, p<0.05; 0.70 ± 0.09 n=6 vs 0.96 ± 0.08 n=6, p =0.05, respectively). Aortic SIRT3 protein expression was negatively correlated aPWV (R=−0.7798, p<0.005). Furthermore, SIRT3 KO male mice demonstrated higher aPWV compared to age‐matched control mice (480±20.77 n=6 vs. 391.3±12.3 n=7, p<0.005). Downstream markers of SIRT3 regulatory activity were examined. Taken together, these data suggest that the age‐associated decline in SIRT3 contributes to increased arterial stiffness and may be a potential target for improving vascular function.Support or Funding InformationSupported by NIH K01AG047626 and University of Iowa Department of Health and Human Physiology.