Sirtuin regulation of metabolism and stem cells - Danica Chen
The metabolic network is coordinately regulated in response to nutritional status to maintain homeostasis. Perturbed metabolic homeostasis is integral to the aging process and underlies many aging-associated diseases. Recent studies strongly suggest that metabolic enzymes are concertedly regulated via acetylation to allow coordination of the directionality and the rate of the metabolic flux upon changes in nutritional status. This mode of metabolic regulation is conserved evolutionarily and is regulated by the sirtuin family of deacetylase. SIRT3, a mammalian mitochondrial sirtuin, regulates the global acetylation landscape of mitochondrial proteins and triggers a metabolic reprogramming to reduce oxidative stress. SIRT3 regulation of oxidative stress has profound physiological relevance, such as stem cell maintenance and tissue homeostasis at an old age, and prevents many aging-associated diseases, including cancer, heart failure, and hearing loss. The SIRT3 regulatory program is suppressed with aging and, intriguingly, SIRT3 reactivation is an effective means of rejuvenation. SIRT7, a mammalian nuclear sirtuin, senses nutritional status and functions at the chromatin to epigenetically regulate metabolic homeostasis.