Fat tissue and long life.

Studies over the last several years have revealed important roles of the body fat content, caloric intake and nutrition, insulin/IGF-1 signaling systems, and pathways involved in oxidative stress and control of protein acetylation on life span. Although the discovery of longevity genes supports the concept that life span is genetically determined, adipose tissue seems to be a pivotal organ in the aging process and in the determination of life span. Leanness and caloric restriction have been shown to increase longevity in organisms ranging from yeast to mammals. Increased longevity in mice with a fat-specific disruption of the insulin receptor gene (FIRKO) suggests that reduced adiposity, even in the presence of normal or increased food intake, leads to an extended life span. Reduced fat mass has an impact on longevity in a number of other model organisms. In Drosophila, a specific reduction in the fat body through overexpression of forkhead type transcription factor (dFOXO) extends life span. Sirtuin 1 (SIRT1), the mammalian ortholog of the life-extending yeast gene silent information regulator 2 (SIR2), was proposed to be involved in the molecular mechanisms linking life span to adipose tissue. Moreover, in the control of human aging and longevity, one of the striking physiological characteristics identified in centenarians is their greatly increased insulin sensitivity even compared with younger individuals. On the other hand, overweight and obesity seem to be associated with decreased life span in humans. In addition, it was recently shown that modifiable risk factors during the later years of life, including smoking, obesity, and hypertension, are associated not only with lower life expectancy, but also with poor health and function during older age. There is growing evidence that the effect of reduced adipose tissue mass on life span could be due to the prevention of obesity-related metabolic disorders including type 2 diabetes and atherosclerosis.