Senotherapeutics for Age-Related Musculoskeletal Disorders: A Systematic Review of Preclinical Evidence

Aging is an important risk factor for musculoskeletal disorders such as osteoarthritis, osteoporosis, and sarcopenia. Cellular senescence contributes to age-related tissue deterioration by promoting functional alterations and a pro-inflammatory environment, making senotherapeutics promising strategies to selectively eliminate senescent cells or limit their deleterious effects. Our systematic review synthesized the available preclinical evidence on the efficacy of senotherapeutics in murine models of osteoarthritis, osteoporosis, and sarcopenia, analyzing structural and functional outcomes and the main molecular mechanisms involved in the regulation of cellular senescence. A literature search was conducted in the MEDLINE, Scopus, and Web of Science databases according to PRISMA guidelines, while the methodological quality of the included studies was assessed using the SYRCLE RoB tool. 26 experimental studies were included, of which 15 involved osteoarthritis models, 6 osteoporosis models, and 5 sarcopenic models. Overall, senotherapeutics demonstrated protective effects on musculoskeletal tissues by reducing inflammation and improving the evaluated outcomes through the modulation of pathways associated with cellular senescence. However, the heterogeneity of experimental models, therapeutic protocols, and outcome measures limits the possibility of drawing definitive conclusions. Further studies will be necessary to clarify the molecular mechanisms involved, optimize therapeutic strategies, and promote the translation of experimental evidence into clinical practice.