Sirtuins, specifically SIRTs, are essential proteins that influence various cellular processes, such as mitochondrial function and genome integrity. In mammals, seven variants of sirtuins (SIRT1-SIRT7) have been identified so far, with SIRT1 being the most thoroughly researched.
Many studies have emphasized the connection between SIRT1 and protection against cardiometabolic disorders. However, there is a lack of evidence regarding the precise role of this protein in human vascular health. A recent study in the journal Nutrients investigated the impact of activating SIRT1 through resveratrol and restricting calorie intake on vascular reactivity in both men and women.
Conclusions
The study concluded that 500 mg of resveratrol per day brought SIRT1 to a similar level as a strict calorie-restricted diet.
The initial SIRT1 gene expression was positively correlated with changes in FMD, indicating that individuals with higher initial SIRT1 gene expression have better FMD. This association was also observed in men.
The results suggest that calorie restriction may improve FMD in men by increasing circulating SIRT1 and reducing BMI. Future research should involve more SIRT1-related biomarkers for a deeper understanding of vascular and metabolic functions.
Introduction
The endothelium plays a crucial role in maintaining vascular stability, both as a physical barrier and an active regulator. Several studies have demonstrated a direct link between endothelial dysfunction and risk factors for developing atherosclerosis.
To assess endothelial function, parameters of vascular reactivity such as vasodilation induced by nitroglycerin (NMD) and flow-mediated dilation (FMD) are used, which are valuable for predicting cardiometabolic events in at-risk groups.
Oxidative stress plays a key role in the development of endothelial dysfunction, with decreased production and availability of nitric oxide (NO) under stress.
FMD, a process dependent on the endothelium, reflects the ability of an artery to relax under stress after obstruction, and is negatively correlated with cardiovascular risks and factors such as high blood lipids, BMI, and smoking. In individuals at high risk, low FMD also indicates worse endothelium-dependent relaxation of coronary arteries.
The regulation of vascular reactivity, including vasoconstriction and vasodilation, is partly controlled by the activation of the sympathetic nervous system via alpha1 and beta2 adrenergic receptors. Impaired beta-adrenergic signaling, often associated with aging, high blood pressure, heart disease, obesity, metabolic syndrome, and diabetes, results in increased release of noradrenaline and a chronic state of vasoconstriction.
Animal studies have shown that SIRT contributes to longer lifespan. SIRT1, which depends on nicotinamide adenine dinucleotide NAD+, acts as a protein deacetylase with antioxidant and anti-inflammatory properties. Laboratory studies have shown that SIRT1 has a sympatholytic effect and improves cardiovascular health.
In animals, calorie restriction leads to activation of SIRT1, which may extend lifespan. However, maintaining such restricted diet in the long term can be challenging.
Various foods and substances, including resveratrol - a polyphenolic compound present in berries, grapes, and peanuts - have shown the ability to activate SIRT1. Previous research has shown that resveratrol has positive effects on cardiometabolic indicators, such as lowering blood lipids, improving glucose metabolism, and reducing blood pressure.
About the Study
In a randomized trial, the effect of SIRT1 activation through supplementation with resveratrol and calorie restriction on vascular reactivity in healthy adult men and women was examined.
This trial included 48 healthy participants to investigate the impact of 500 mg of resveratrol per day and an energy restriction of 1,000 kcal per day for 30 days on vascular reactivity parameters and SIRT1.
The group consisted of 24 postmenopausal women and 24 men aged 55 to 65 years, without a history of cardiovascular disease or chronic diseases.
Participants underwent a 15-day washout period without medication or supplements before being randomly assigned to calorie restriction or resveratrol groups, divided by gender.
Biochemical parameters such as triglycerides, HDL-c, total cholesterol, apoA-I, LDL-c, apoB, NEFA, Lp(a), glucose, insulin, SIRT1 gene expression, hsCRP, noradrenaline, and serum levels, along with estimates of both endothelium-dependent and -independent vasodilation, were measured.
Study Results
The study showed that 30 days of both energy restriction and supplementation with 500 mg of resveratrol per day increased circulating SIRT1 levels and reduced plasma NA levels.
Before the interventions, a strong association was observed between the reduction in plasma NA and higher SIRT1 levels. After 30 days, SIRT1 levels were positively correlated with NMD, regardless of gender and type of intervention.
In the calorie restriction group, an independent association between circulating SIRT1 and NMD was observed. Although no significant differences in SIRT1 gene expression were found, there was a significant association with FMD in men.
Mechanically, calorie restriction leads to SIRT1 activation by reducing glycolytic processes, promoting respiratory metabolism, stimulating NAD+ replenishment and NADH reduction, and increasing the expression of PNC1 and Nampt.
Source:
Sirtuin 1 and Vascular Function in Healthy Women and Men: A Randomized Clinical Trial Comparing the Effects of Energy Restriction and Resveratrol. Nutrients. Gonçalinho, G. H. F., Kuwabara, K. L., de Oliveira Faria, N. F., et al. (2023). doi:10.3390/nu15132949.
https://www.mdpi.com/2072-6643/15/13/2949
