Sirtuins: exploring next-gen therapeutics in the pathogenesis osteoporosis and associated diseases

OBJECTIVE: Osteoporosis poses a substantial public health challenge due to an ageing population and the lack of adequate treatment options. The condition is marked by a reduction in bone mineral density, resulting in an elevated risk of fractures. The reduction in bone density and strength, as well as musculoskeletal issues that come with aging, present a significant challenge for individuals impacted by these conditions, as well as the healthcare system worldwide. METHODS: Literature survey was conducted until May 2023 using databases such as Web of Science, PubMed, Scopus, and Google Scholar. RESULT: Sirtuins 1-7 (SIRT1-SIRT7), which are a group of Nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, possess remarkable capabilities to increase lifespan and combat diseases related to aging. Research has demonstrated that these proteins play an important role in regular skeletal development and maintenance by directly impacting bone cells. Their dysfunction could be a factor in various bone conditions. Studies conducted on animals before clinical trials have shown that administering Sirtuins agonists to mice provides a safeguard against osteoporosis resulting from aging, menopause, and immobilization. These findings imply that Sirtuins may be a viable target for addressing the irregularity in bone remodeling and treating osteoporosis and other skeletal ailments. CONCLUSION: The purpose of this review was to present a thorough and current evaluation of the existing knowledge on Sirtuins biology, with a particular emphasis on their involvement in maintaining bone homeostasis and contributing to osteoporosis. Additionally, the review examines potential pharmacological interventions targeting Sirtuins for the treatment of osteoporosis.