Exploring cellular senescence in the musculoskeletal system: Any insights for biomarkers discovery?

The locomotor system comprises skeletal muscles and bones with active metabolism and cellular turnover. Chronic locomotor system disorders gradually arising with aging are inversely associated with the correct function of bone and muscles. Senescent cells appear more frequently in advanced ages or pathological conditions, and the accumulation of senescent cells in muscle tissue negatively correlates with muscle regeneration, which is crucial for maintaining strength and preventing frailty. Senescence in the bone microenvironment, osteoblasts, and osteocytes affects bone turnover favoring osteoporosis. It is likely that in response to injury and age-related damage over the lifetime, a subset of niche cells accumulates oxidative stress and DNA damage beyond the threshold that primes the onset of cellular senescence. These senescent cells may acquire resistance to apoptosis that, combined with the weakened immune system, results in impaired clearance of senescent cells and their accumulation. The secretory profile of senescent cells causes local inflammation, further spreading senescence in neighboring niche cells and impairing tissue homeostasis. The resulting impairment of turnover/tissue repair in the musculoskeletal system reduces the efficiency of the organ in response to environmental needs that finally lead to functional decline. Management of the musculoskeletal system at the cellular level can benefit the quality of life and reduce early aging. This work discusses current knowledge of cellular senescence of musculoskeletal tissues to conclude with biologically active biomarkers effective enough to reveal the underlying mechanisms of tissue flaws at the earliest possible.