Reduced SIRT3 contributes to large elastic artery stiffness with aging

During the 20th Century the United States saw a change in the leading causes of death, with a shift from infectious diseases such as tuberculosis, pneumonia, and influenza to chronic diseases associated with aging such as cardiovascular disease (Centers for Disease Control). Recent research has unveiled Sirtuin 3 (SIRT3), a protein that requires NAD⁺ as a substrate, as a major player in age-related diseases throughout the body. The goal of this thesis was to measure SIRT3 protein and NAD⁺ levels in young and old male mice, and to determine if aging causes changes that has meaningful impact on vascular function, such aortic stiffness, which is both a risk factor and predictor of cardiovascular diseases. Finally, we investigated whether increasing NAD⁺ with a recently discovered form of vitamin B3, nicotinamide riboside, could increase NAD⁺ concentration in tissue and reverse age-related aortic stiffening.

We found that SIRT3 was associated with increased aortic stiffness perhaps due to age-related decreases in NAD⁺. Furthermore, mice deficient in SIRT3 had increased aortic stiffness compared to their age-matched counterparts, indicating that SIRT3 plays a role in maintenance of healthy arteries. Long term NR supplementation increased NAD⁺ concentration in kidney tissue in old mice, but did not have an effect on age associated arterial stiffness. We show here for the first time that supplementation with NR restores NAD⁺ levels in the kidney with aging, indicating therapeutic potential in kidney disease.