We conclude that, contrary to some previous reports, the mechanism by which SIRT1 regulates mitochondrial biogenesis is by inhibiting PGC-1α coactivator activity, resulting in a decrease in mitochondria. We also conclude that feeding rodents resveratrol has no effect on mitochondrial biogenesis in muscle.
Aging is thought to be associated with decreased vascular function partly due to oxidative stress. Resveratrol is a polyphenol, which, in animal studies has been shown to decrease atherosclerosis, improve cardiovascular health and physical capacity, in part through its effects on Sirtuin 1 signaling and through an improved antioxidant capacity. We tested the hypothesis that resveratrol supplementation enhances training-induced improvements in cardiovascular health parameters in aged men. Twenty-seven healthy physically inactive aged men (age: 65 ± 1 years; BMI: 25.4 ± 0.7 kg/m2; MAP: 95.8 ± 2.2 mmHg; maximal oxygen uptake: 2488 ± 72 ml O2 min-1) were randomized into 8 weeks of either daily intake of either 250 mg trans resveratrol (n = 14) or of placebo (n = 13) concomitant with high-intensity exercise training. Exercise training lead to a 45% greater (P < 0.05) increase in maximal oxygen uptake in the placebo group than in the resveratrol group and to a decrease in MAP in the placebo group only (-4.8 ± 1.7 mmHg; P < 0.05). The interstitial level of vasodilator prostacyclin was lower in the resveratrol than in the placebo group after training (980 ± 90 versus 1174 ± 121 pg ml-1; P < 0.02) and muscle TBX synthase was higher in the resveratrol group after training (P < 0.05). Resveratrol administration also abolished the positive effects of exercise on LDL, TC/HDL ratio and triglycerides concentrations in blood (P < 0.05). Resveratrol did not potentiate the effect of exercise training on atherosclerosis marker VCAM-1. Sirtuin 1 protein levels were not affected by resveratrol supplementation. These findings indicate that, whereas exercise training effectively improves several cardiovascular health parameters in aged men, concomitant resveratrol supplementation blunts most of these effects.
This is an unusual finding, not what the researchers expected. Nevertheless, it looks like it’s time for a reevaluation of resveratrol.