Cellular senescence as a key factor in osteoporosis: the role of SIRT1

Osteoporosis, a prevalent age-related condition, is characterized by decreased in bone mass and bone quality. Among the pathogenetic mechanisms, cellular senescence has been suggested to induce inflammation and affect bone cell function, contributing to bone fragility. In this context, sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, emerges as a central regulator of musculoskeletal health, influencing osteoblastic differentiation, suppressing osteoclastic activity and maintaining bone mass by the deacetylation of critical targets. Interestingly, a close association was found between an elevated senescence-associated secretory phenotype and aged bone cells, confirming a role for senescence in bone aging. The aim of our minireview is to highlight cellular senescence as a key factor in osteoporosis, focusing on the central role of SIRT1 and exploring potential strategies to modulate its activity, including diet, exercise and pharmacological interventions. In conclusion, enhancing SIRT1 activity represents a potential therapeutic approach for age-related bone disorders, offering interesting perspectives for future research and therapeutic development. KEY WORDS: SIRT1, osteoporosis aging senescence bone cells, diet, exercise, pharmacological interventions.