White adipose tissue now emerges as a pivotal organ controlling lifespan. Calorie restriction, which so far extends lifespan in all organisms, primarily affects energy stores in adipose tissue. Genetic manipulations aiming at modifying fat mass also impact on the duration of life in several model organisms. We recently proposed that silent information regulator 2 (SIR2) ortholog, sirtuin 1 (SIRT1), the mammalian ortholog of the life-extending yeast gene SIR2, is involved in the molecular mechanisms linking lifespan to adipose tissue. SIRT1 represses peroxisome proliferator-activated receptors gamma transactivation and inhibits lipid accumulation in adipocytes. The effect of adipose tissue reduction on lifespan could be due to the production of adipokines acting on target tissues such as the brain, or due to the indirect prevention of age-related metabolic disorders like type 2 diabetes or atherosclerosis.
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