Resveratrol and Sirt 1 activators for the treatment of aging and age-related diseases

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.