Sirtuin 1 and Vascular Function in Healthy Women and Men: A Randomized Clinical Trial Comparing the Effects of Energy Restriction and Resveratrol

Abstract

Background: Sirtuin 1 (SIRT1) has been associated with longevity and protection against cardiometabolic diseases, but little is known about how it influences human vascular function. Therefore, this study evaluated the effects of SIRT1 activation by resveratrol and energy restriction on vascular reactivity in adults. Methods: A randomized trial allocated 48 healthy adults (24 women and 24 men), aged 55 to 65 years, to resveratrol supplementation or energy restriction for 30 days. Blood lipids, glucose, insulin, C-reactive protein, noradrenaline, SIRT1 (circulating and gene expression), and flow-mediated vasodilation (FMD) and nitrate-mediated vasodilation (NMD) were measured. Results: Both interventions increased circulating SIRT1 (p < 0.001). Pre- and post-tests changes of plasma noradrenaline were significant for both groups (resveratrol: p = 0.037; energy restriction: p = 0.008). Baseline circulating SIRT1 was inversely correlated with noradrenaline (r = −0.508; p < 0.01), and post-treatment circulating SIRT1 was correlated with NMD (r = 0.433; p < 0.01). Circulating SIRT1 was a predictor of FMD in men (p = 0.045), but not in women. SIRT1 was an independent predictor of NMD (p = 0.026) only in the energy restriction group. Conclusions: Energy restriction and resveratrol increased circulating SIRT1 and reduced sympathetic activity similarly in healthy adults. SIRT1 was independently associated with NMD only in the energy restriction group.

Energy availability modulates regional blood flow via estrogen-independent pathways in regularly menstruating young women

“…We found no correlation between change in REE and FFM during LEA and suggest that downregulated tissue function (not loss of mass) may be responsible. In support of this, previous research has shown that lower REE in exercise-associated amenorrhea is not due to reduced tissue mass (Gonçalinho et al 2023). These findings identify that metabolic allostasis can occur rapidly during LEA and underscore the importance of using measures other than changes in body mass to indicate energy status.…”

“…For the first time, we demonstrate that in eumenorrheic non-exercising women assessed during the low-hormone phase of the menstrual cycle, resting FBF is decreased with just 3-days LEA. We also identify an association between resting FBF and REE, which may offer mechanistic insights into metabolic allostasis in response to LEA (Gavin et al 2009;Gonçalinho et al 2023).…”

“…LEA lasting several months can cause menstrual disturbances such as amenorrhea (the cessation of menses for ≥ 90 days) via suppression of the hypothalamic-pituitary-ovarian axis, which is characterized by chronic estrogen deficiency (Forstermann and Munzel 2006;Freedson et al 1998;Gavin et al 2009). Exercising women with amenorrhea exhibit reduced resting energy expenditure (REE) commensurate with downregulated physiological function and energy conservation in response to LEA (Gonçalinho et al 2023). An association between LEA and impaired cardiovascular function exists in this population (Greenfield et al 1963;Headland et al 2019;Heikura et al 2018).…”

The Effect of Diet on Vascular Aging: A Narrative Review of the Available Literature

“…According to the RCT by Gonçalinho et al [62], endothelium-dependent FMD and endothelium-independent vasodilation (NMD) were assessed in a group of healthy subjects randomized to either receive a resveratrol supplement (500 mg/day) or a low-calorie diet (1000 kcal/day, providing over 50% energy restriction). An absence of difference was observed both for the FMD and the NMD (p = 0.443; p = 0.196, respectively), between the baseline and the post-treatment assessment, regarding the energy restriction group [62].…”

Understanding the role of sirtuin 1 in muscle physiology during androgen deprivation

“…These supplements could function as SIRT activators, enhancing the pharmacological perspective of SIRT use. Researchers have sought to investigate the role of SIRT1 in vascular function, in cardioprotection and in the metabolic properties of skeletal muscle relating to mitochondrial function and muscle fibre properties (Gonçalinho et al., 2023). Despite these efforts, further investigations are needed to better elucidate the mechanisms and therapeutic possibilities of SIRT1.…”