Abstract <p>The increasing number of people aged 65 and older is an irreversible global trend. The growing number of studies increase confidence that classical age-associated diseases and geriatric conditions share a common set of basic biological mechanisms. Many endogenous molecules counteract the mechanisms of cellular senescence. To date, a number of anti-aging molecules have been identified, the role of which has been assessed in the pathophysiology of different diseases. NAD-dependent protein deacetylases and ADP-ribosyltransferases from the sirtuin family are considered as potential factors that slow down aging. Sirtuins are associated with antioxidant and oxidative stress reactions, regulation of mitochondrial function, repair of DNA damage and metabolism. Sirtuins and associated signaling cascades of cellular senescence regulatory network have a considerable impact on the development of age-associated diseases. The review presents a comprehensive analysis of the results of basic and clinical studies to shed the newlight on the role of sirtuins in the processes of cellular senescence and in the development of age-associated diseases. The data on the mechanisms of cellular senescence, the function of sirtuins (SIRT1−7), their interaction with key regulators of signaling cascades of cellular senescence and data on the association of polymorphic variants of sirtuin genes with the development of multifactorial diseases and longevity are presented.</p>