Cellular senescence and the skeleton: pathophysiology and therapeutic implications

Cellular senescence is a fundamental aging mechanism that is currently the focus of considerable interest as a pathway that could be targeted to ameliorate aging across multiple tissues, including the skeleton. There is now substantial evidence that senescent cells accumulate in the bone microenvironment with aging and that targeting these cells prevents age-related bone loss, at least in mice. Cellular senescence also plays important roles in mediating the skeletal fragility associated with diabetes mellitus, radiation, and chemotherapy. As such, there are ongoing efforts to develop senolytic drugs that kill senescent cells by targeting key survival mechanisms in these cells without affecting normal cells. Because senescent cells accumulate across tissues with aging, senolytics offer the attractive possibility of treating multiple age-related comorbidities simultaneously.

Automated summary

Cellular senescence is a key mechanism in aging, especially in the skeletal system, and targeting senescent cells shows promise in preventing age-related bone loss and fragility. Efforts are underway to develop senolytic drugs that specifically kill senescent cells while sparing normal cells, offering a potential treatment for multiple age-related comorbidities.