Exercise improves health, but why? Many researchers are digging into the biochemical details, such as the authors of the paper referenced here, who focus on tendon integrity and its deterioration in aging, a degenerative process that is slowed by exercise. Overall regular moderate exercise is comprehensively demonstrated to improve long-term health and raise median life span in animal studies, and is robustly associated with better health, lower medical expenditures, and increased life expectancy in human epidemiological studies.
In recent years, a few studies have been performed to better understand the cellular and molecular mechanisms responsible for the effects of aging on tendons. In general, aging slowly lowers the functional competence of the human body, largely due to the damages in DNA, changes in the cellular microenvironments of the body and epigenetic regulation. In tendons, aging increases the nucleus to cytoplasm ratio and lipid deposition, but decreases vascularization and tendon matrix integrity, and alters tendon cell's response to cellular stimuli. In addition, aging also reduces the number of tendon cells and decreases their activity thereby depleting the resources required to repair injured tendons. Consequently, there is a steady decline in the ability of tendons to repair its injuries over time. Through these changes aging reduces the mechanical strength of tendons and makes them susceptible to injuries, thus lowering the quality of life of the aging population and increasing the healthcare cost.
While aging generally causes detrimental effects on tendons, exercise is known to exert beneficial effects on tendons. Traditionally, tendons were considered to contain only one cell type, the tenocytes, which are resident fibroblast-like cells that maintain tendon integrity, remodeling and repair. However, a new tendon cell type, termed tendon stem/progenitor cells (TSCs), has been identified in recent years in humans, rabbits, mice, and rats. However, the role of TSCs in aging- and exercise-induced changes in tendons is not well understood. Therefore, to explore the TSC-based mechanisms responsible for the beneficial effects of exercise on aging tendons, we tested two hypotheses in this study: i) aging impairs TSC function in tendons, and ii) moderate exercise revives impaired TSC function and thereby exerts beneficial effects on aging tendons.
TSCs derived from aging mice (9 and 24 months) proliferated significantly slower than TSCs obtained from young mice (2.5 and 5 months). In addition, expression of the stem cell markers Oct-4, nucleostemin (NS), Sca-1 and SSEA-1 in TSCs decreased in an age-dependent manner. Interestingly, moderate mechanical stretching (4%) of aging TSCs in vitro significantly increased the expression of the stem cell marker, NS, but 8% stretching decreased NS expression. In the in vivo study, moderate treadmill running of aging mice (9 months) resulted in the increased proliferation rate of aging TSCs in culture, decreased lipid deposition, proteoglycan accumulation and calcification, and increased the expression of NS in the patellar tendons. These findings indicate that while aging impairs the proliferative ability of TSCs and reduces their stemness, moderate exercise can mitigate the deleterious effects of aging on TSCs and therefore may be responsible for decreased aging-induced tendon degeneration.