Sirtuins are a conserved family of proteins found across all domains of life, initially discovered in *Saccharomyces cerevisiae* as Sir2. These proteins regulate various cellular processes, including DNA recombination, gene silencing, DNA repair, chromosomal stability, and longevity. Sir2 homologues in other organisms, such as worms and flies, also modulate lifespan, suggesting a potential role in the beneficial effects of caloric restriction, the only regimen known to slow aging and extend lifespan in most organisms, including mammals. The seven mammalian sirtuins (SIRT1–7) have gained significant attention for their impact on aging and age-related diseases, making them potential targets for therapeutic interventions. The functions of mammalian sirtuins are diverse and include chromatin structure and transcription regulation, apoptosis and cell survival, stress resistance, DNA repair, HIV-1 replication, ion channel regulation, development, inflammation, and energy metabolism. For example, SIRT1 facilitates heterochromatin formation, regulates p53-dependent apoptosis, and modulates energy metabolism. SIRT6 is involved in base excision repair, while SIRT4 regulates amino-acid-stimulated insulin secretion. SIRT2 may suppress brain tumors, and SIRT3 and SIRT4 play key roles in mitochondrial function and metabolic pathways. The discovery of sirtuin activators, such as resveratrol, has opened new avenues for exploring their potential in extending lifespan and improving health in mammals. Resveratrol has been shown to extend lifespan in various organisms and modulate cellular processes in a SIRT1-dependent manner. Studies in mice have demonstrated that resveratrol can shift the physiological state towards that of lean mice, enhancing mitochondrial function, reducing blood glucose and insulin levels, and improving metabolic profiles. Overall, the extensive research on sirtuins has revealed their critical roles in various biological processes, highlighting their potential as therapeutic targets for age-related diseases and longevity interventions.Sirtuins are a conserved family of proteins found across all domains of life, initially discovered in *Saccharomyces cerevisiae* as Sir2. These proteins regulate various cellular processes, including DNA recombination, gene silencing, DNA repair, chromosomal stability, and longevity. Sir2 homologues in other organisms, such as worms and flies, also modulate lifespan, suggesting a potential role in the beneficial effects of caloric restriction, the only regimen known to slow aging and extend lifespan in most organisms, including mammals. The seven mammalian sirtuins (SIRT1–7) have gained significant attention for their impact on aging and age-related diseases, making them potential targets for therapeutic interventions. The functions of mammalian sirtuins are diverse and include chromatin structure and transcription regulation, apoptosis and cell survival, stress resistance, DNA repair, HIV-1 replication, ion channel regulation, development, inflammation, and energy metabolism. For example, SIRT1 facilitates heterochromatin formation, regulates p53-dependent apoptosis, and modulates energy metabolism. SIRT6 is involved in base excision repair, while SIRT4 regulates amino-acid-stimulated insulin secretion. SIRT2 may suppress brain tumors, and SIRT3 and SIRT4 play key roles in mitochondrial function and metabolic pathways. The discovery of sirtuin activators, such as resveratrol, has opened new avenues for exploring their potential in extending lifespan and improving health in mammals. Resveratrol has been shown to extend lifespan in various organisms and modulate cellular processes in a SIRT1-dependent manner. Studies in mice have demonstrated that resveratrol can shift the physiological state towards that of lean mice, enhancing mitochondrial function, reducing blood glucose and insulin levels, and improving metabolic profiles. Overall, the extensive research on sirtuins has revealed their critical roles in various biological processes, highlighting their potential as therapeutic targets for age-related diseases and longevity interventions.