Calorie restriction mimetics and aging

Abstract

Various polyphenols found in plants are able to activate biochemical pathways in mammalian cells so as to confer health benefits. These molecules include resveratrol, catechins, quercetin and genistein. There is considerable overlap between these pathways and those activated by caloric restriction. The chemicals have therefore been termed calorie restriction mimetics. In both cases the response induced steels the cell to resist adverse or stressful conditions. In the present chapter the effects of some of the most well studied compounds will be described. As a result of their effects cells become more resistant to oxidative stress, inflammatory pathways are suppressed, and changes are seen in the cell cycle. Resveratrol has been shown to extend lifespan in various organisms and to extinguish disease processes in obese mice, so that instead of dying early, the mice have a normal lifespan. The changes induced seem in large part to be mediated by their activation of sirtuin enzymes. Sirtuins deacetylate and thereby activate transcription factors that alter the expression of various genes involved in stress-resistance. The enormous potential that natural and synthetic sirtuin activating compounds have in prevention and treatment of type 2 diabetes, cardiovascular disease, dementia and cancer without side effects makes them of considerable topical interest clinically. Synthetic compounds whose sirtuin-activating ability is a thousand times stronger than resveratrol have been discovered and represent potential new drugs to combat common diseases of aging.