Sirtuins are a family of NAD+-dependent enzymes that regulate lifespan in lower organisms. Recent research has shown that mammalian sirtuins are involved in various biological processes, including cellular stress resistance, genomic stability, tumorigenesis, and energy metabolism. This review summarizes recent progress in understanding sirtuin biology, their role in age-related diseases, and the potential link between sirtuin activity and lifespan regulation. The sirtuin family was first identified in yeast, where Sir2 was found to regulate lifespan and genomic stability. Subsequent studies in other organisms, including Caenorhabditis elegans and Drosophila, confirmed the role of sirtuins in lifespan extension. In mammals, seven sirtuins have been identified, with SIRT1 being the most studied. These proteins are localized to different subcellular compartments and are involved in various cellular processes, including DNA repair, cell fate, and metabolic regulation. Sirtuins play a crucial role in DNA repair by deacetylating histone proteins and maintaining genomic stability. They also regulate cellular stress resistance and modulate the threshold for cell death. SIRT1 interacts with the Forkhead box class O (FOXO) family of transcription factors, which regulate energy status and stress resistance. SIRT1 can also protect cells against stress by regulating the heat shock response and modulate the threshold for cell death in the setting of exogenous stress. Sirtuins are involved in metabolic regulation, including glucose homeostasis and insulin secretion. SIRT1 regulates the activity of PPAR-γ and PGC-1α, which are involved in fat mobilization and fatty acid oxidation. SIRT1 also plays a role in mitochondrial biogenesis and autophagy. In addition, SIRT1 can regulate the urea cycle and other metabolic pathways. Sirtuins are also involved in age-related diseases, including cancer and cardiovascular disease. SIRT1 has been shown to regulate p53 activity, which is involved in tumorigenesis. SIRT1 can also protect against oxidative stress and neurodegeneration. However, the role of sirtuins in these diseases is complex, with some studies suggesting that increased sirtuin activity may promote or prevent tumorigenesis. Overall, sirtuins are important regulators of cellular fate and mammalian physiology. While much remains to be understood, the potential of sirtuins in regulating lifespan and metabolic diseases is promising. Current research is exploring the use of sirtuin activators as potential therapies for metabolic and age-related diseases.Sirtuins are a family of NAD+-dependent enzymes that regulate lifespan in lower organisms. Recent research has shown that mammalian sirtuins are involved in various biological processes, including cellular stress resistance, genomic stability, tumorigenesis, and energy metabolism. This review summarizes recent progress in understanding sirtuin biology, their role in age-related diseases, and the potential link between sirtuin activity and lifespan regulation. The sirtuin family was first identified in yeast, where Sir2 was found to regulate lifespan and genomic stability. Subsequent studies in other organisms, including Caenorhabditis elegans and Drosophila, confirmed the role of sirtuins in lifespan extension. In mammals, seven sirtuins have been identified, with SIRT1 being the most studied. These proteins are localized to different subcellular compartments and are involved in various cellular processes, including DNA repair, cell fate, and metabolic regulation. Sirtuins play a crucial role in DNA repair by deacetylating histone proteins and maintaining genomic stability. They also regulate cellular stress resistance and modulate the threshold for cell death. SIRT1 interacts with the Forkhead box class O (FOXO) family of transcription factors, which regulate energy status and stress resistance. SIRT1 can also protect cells against stress by regulating the heat shock response and modulate the threshold for cell death in the setting of exogenous stress. Sirtuins are involved in metabolic regulation, including glucose homeostasis and insulin secretion. SIRT1 regulates the activity of PPAR-γ and PGC-1α, which are involved in fat mobilization and fatty acid oxidation. SIRT1 also plays a role in mitochondrial biogenesis and autophagy. In addition, SIRT1 can regulate the urea cycle and other metabolic pathways. Sirtuins are also involved in age-related diseases, including cancer and cardiovascular disease. SIRT1 has been shown to regulate p53 activity, which is involved in tumorigenesis. SIRT1 can also protect against oxidative stress and neurodegeneration. However, the role of sirtuins in these diseases is complex, with some studies suggesting that increased sirtuin activity may promote or prevent tumorigenesis. Overall, sirtuins are important regulators of cellular fate and mammalian physiology. While much remains to be understood, the potential of sirtuins in regulating lifespan and metabolic diseases is promising. Current research is exploring the use of sirtuin activators as potential therapies for metabolic and age-related diseases.