What Are Sirtuins and How Do They Affect Aging and Longevity?

Sirtuins facilitate adaptive metabolic responses during periods of fasting, caloric restriction, and exercise. For example, SIRT1 acts as an autophagy modulator through the deacetylation of major transcription factors like peroxisome-activated receptor coactivator 1-#945; (PGC-1#945;) and forkhead box O3 (FoxO3) proteins, thereby enhancing fatty acid oxidation and glucose production in the liver. In skeletal muscles, SIRT1 has been associated with mitochondrial biogenesis and improved insulin sensitivity to support systemic metabolic health. Skeletal-muscle sirtuins also regulate glucose uptake, fatty acid oxidation, mitochondrial dynamics, autophagy, myogenesis, fiber-type switching, regeneration, and exercise adaptation, although these effects remain isoform- and context-dependent.