Resveratrol and SIRT1 Activators for the Treatment of Aging and Age-Related Diseases

Abstract

Reduced calorie intake is a religious and medical practice known since very old times, but its direct influence on life span in all organisms, included humans, has been demonstrated in the modern era. Not only periodic fasting, but also natural or synthetic compounds that mimic this phenomenon are growing to slow aging and the onset of chronic morbidities. Resveratrol (RSV), a plant polyphenol, is an elixir of longevity for simple organisms and preclinical rodent models even if a beneficial role in humans is still debated. Its main rejuvenating mechanism copes with the activation of specific longevity genes called sirtuins. Among seven known mammalian sirtuins, sirtuin 1 is the most studied. This pleiotropic nicotinamide adenine dinucleotide (NAD)-based deacetylase maintains longevity by removing acetyl group in nuclear histones, transcription factors, and other DNA repairing proteins. Actually, an exciting challenge is to discover and test novel sirtuin 1 activators to extend life span and to treat age-associated disabilities. This chapter updates on the antiaging effect of RSV and sirtuin 1 activators in experimental animals and in humans. Finally, pros and cons on RSV analogues and sirtuin 1 activators tested in preclinical and clinical trials to hamper neurological deficit, cardiovascular complications, diabetes, bone and muscle deterioration, and cancer are discussed.

Grape Cane Extracts as Multifunctional Rejuvenating Cosmetic Ingredient: Evaluation of Sirtuin Activity, Tyrosinase Inhibition and Bioavailability Potential

“…In yeast, E-resveratrol mimics calorie restriction by the stimulation of SIR2, increasing DNA stability and extending lifespan by 70%. Stacchiotti et al (2016) [22] confirmed that the first function of E-resveratrol is to reduce inflammation and to limit oxidative damage in tissues. The antiaging properties of E-resveratrol via SIRT1 activation are also associated to oxidative metabolism improvement in crucial organs like the heart, vessels, muscles and kidney [22].…”

“…Stacchiotti et al (2016) [22] confirmed that the first function of E-resveratrol is to reduce inflammation and to limit oxidative damage in tissues. The antiaging properties of E-resveratrol via SIRT1 activation are also associated to oxidative metabolism improvement in crucial organs like the heart, vessels, muscles and kidney [22]. In other studies, in the presence of a SIRT1 inhibitor like nicotinamide, E-resveratrol stimulated SIRT1 [16].…”

“…Therefore, it can be claimed that polyphenol-rich GCE would be more beneficial in skincare treatments than encapsulated pure stilbenoids [22]. Further experiments on skin models are still required to confirm the potential of GCE as a natural multifunctional ingredient for eco-friendly dermocosmetics.…”

Sirtuin-1 and Its Relevance in Vascular Calcification

“…Sirt1 is linked to extended lifespans and acts as an intracellular energy sensor involved in the pathophysiology of aging [21][22][23] and fatty or non-fatty liver disease. The NAD + /NADH ratio is a key regulator that determines Sirt1 activity.…”

“…Whereas, calorie restriction (CR) conversely increases the NAD + /NADH ratio and, subsequently, increases Sirt1 activity, which is why cumulative evidence supports CR as a possible way to enhance longevity in mammals [26]. Sirt1 is linked to extended lifespans and acts as an intracellular energy sensor involved in the pathophysiology of aging [21][22][23] and fatty or non-fatty liver disease. The NAD + /NADH ratio is a key regulator that determines Sirt1 activity.…”