Indeed, some researchers have suggested that Alzheimer’s and other diseases characterized by neuron death might be “two-hit phenomena” caused not only by protein buildup but also by malfunctions in the molecular pathways that suppress tumors. SIRT1 is connected with tumor suppression, Snyder says, and may point to a second hit necessary for the development of Alzheimer’s. Although he cautions that this is early work, Snyder says that Sinclair and Tsai “seem to have their hands on a potential mechanism.”
Sinclair and Tsai’s findings add to growing evidence that resveratrol could have a broad range of beneficial health effects, from treating metabolic diseases like obesity and diabetes to protecting against neurodegenerative disorders. Previous studies have shown that resveratrol extends life span in yeast, roundworms, fruit flies, and fish. (See “A Life-Extending Pill for Fat Mice.”) Researchers don’t know exactly how it causes health benefits and prolongs life span, but it appears to activate SIRT1. This gene is one of a family of genes called sirtuins that many researchers believe are master regulators of the aging process. By activating sirtuins, Sinclair, Guarente, and other researchers aim not to extend human life but to create new therapies for the diseases of aging. (See “Fountain of Health.”)
“I’m optimistic about SIRT1 activation as a therapeutic,” says Sinclair. “[Its effect] seems to be so broad, as though the gene can keep cells alive under very different types of stress.” Now SIRT1 activation appears to keep neurons alive and reverse cognitive decline, providing further reason for Sirtris and other pharmaceutical companies to continue exploring this therapeutic approach.