Small molecule SIRT1 activators for the treatment of aging and age-related diseases.
Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and challenges surrounding the development of SIRT1 activators, molecules with the potential to delay aging and age-related diseases. Sirtuins comprise a family of NAD⁺-dependent deacylases that are central to the body's response to diet and exercise. New studies indicate that both natural and synthetic sirtuin activating compounds (STACs) work via a common allosteric mechanism to stimulate sirtuin activity, thereby conferring broad health benefits in rodents, primates, and possibly humans. The fact that two-thirds of people in the USA who consume multiple dietary supplements consume resveratrol, a SIRT1 activator, underscores the importance of understanding the biochemical mechanism, physiological effects, and safety of STACs.
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Basil P
BP
Hubbard
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: david_sinclair@hms.harvard.edu.
David A
DA
Sinclair
D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008136:Longevity / Q000187:drug effects / Q000502:physiology; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism*
D056564:Sirtuin 1
STAC; aging; allosteric activator; cancer; cardiovascular disease; chromatin; deacetylase; diabetes; inflammation; sirtuin