The role of sirtuins (SIRT1-SIRT7) in cellular metabolism and aging: A molecular overview

Abstract

Sirtuins (SIRT1-SIRT7), a family of NAD⁺-dependent deacetylases and ADP-ribosyltransferases, have emerged as key regulators of metabolic homeostasis, stress responses, and the aging process in eukaryotic organisms. These highly conserved enzymes influence multiple biological pathways, including DNA repair, mitochondrial function, insulin sensitivity, and inflammation. Their dependence on NAD⁺ links their activity to the cell’s metabolic state, positioning them as metabolic sensors. Sirtuins are localized in different cellular compartments-nucleus, cytoplasm, and mitochondria and each member exhibits unique substrate specificity and physiological roles. This review presents a comprehensive molecular overview of SIRT1 through SIRT7, highlighting their distinct and overlapping functions in cellular metabolism and aging. Furthermore, the potential of targeting sirtuins in age-related diseases and metabolic disorders is discussed, emphasizing the therapeutic promise of sirtuin modulation in promoting healthspan and longevity.