Lifespan and healthspan extension by resveratrol

•Resveratrol activates Sir2 and modulates other targets with important physiological roles.•Resveratrol extends the lifespan of diverse model organisms.•Lifespan and healthspan of metabolically compromised mammals are increased by resveratrol.•Resveratrol may not be an ideal drug candidate, but alternatives exist.•Future studies will need to be carefully designed in order to examine its effects on human lifespan.

A number of small molecules with the ability to extend the lifespan of multiple organisms have recently been discovered. Resveratrol, amongst the most prominent of these, has gained widespread attention due to its ability to extend the lifespan of yeast, worms, and flies, and its ability to protect against age-related diseases such as cancer, Alzheimer's, and diabetes in mammals. In this review, we discuss the origins and molecular targets of resveratrol and provide an overview of its effects on the lifespan of simple model organisms and mammals. We also examine the unique ability of resveratrol to extend the healthy years, or healthspan, of mammals and its potential to counteract the symptoms of age-related disease. Finally, we explore the many scientific, medical, and economic challenges faced when translating these findings to the clinic, and examine potential approaches for realizing the possibility of human lifespan extension. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.