Sirtuin activators: designing molecules to extend life span.
Resveratrol (RESV) exerts important pharmacological effects on human health: in addition to its beneficial effects on type 2 diabetes and cardiovascular diseases, it also modulates neuronal energy homeostasis and shows antiaging properties. Although it clearly has free radical scavenger properties, the mechanisms involved in these beneficial effects are not fully understood. In this regard, one area of major interest concerns the effects of RESV on the activity of sirtuin 1 (SIRT1), an NAD(+)-dependent histone deacetylase that has been implicated in aging. Indeed, the role of SIRT1 is currently the subject of intense research due to the antiaging properties of RESV, which increases life span in various organisms ranging from yeast to rodents. In addition, when RESV is administered in experimental animal models of neurological disorders, it has similar beneficial effects to caloric restriction. SIRT1 activation could thus constitute a potential strategic target in neurodegenerative diseases and in disorders involving disturbances in glucose homeostasis, as well as in dyslipidaemias or cardiovascular diseases. Therefore, small SIRT1 activators such as SRT501, SRT2104, and SRT2379, which are currently undergoing clinical trials, could be potential drugs for the treatment of type 2 diabetes, obesity, and metabolic syndrome, among other disorders. This review summarises current knowledge about the biological functions of SIRT1 in aging and aging-associated diseases and discusses its potential as a pharmacological target.
Camins
Antoni
A
Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, Nucli Universitari de Pedralbes, 08028 Barcelona, Spain. camins@ub.edu
Sureda
Francesc X
FX
Junyent
Felix
F
Verdaguer
Ester
E
Folch
Jaume
J
Pelegri
Carme
C
Vilaplana
Jordi
J
Beas-Zarate
Carlos
C
Pallàs
Mercè
M
D000375:Aging / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D020536:Enzyme Activators / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009474:Neurons / Q000201:enzymology; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000737:chemistry / Q000494:pharmacology; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*
D020536:Enzyme Activators; D013267:Stilbenes; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol