Mechanical and Structural Adaptations of Tendon with Aging.

Abstract

Tendon provides a critical functional link between muscle and the skeleton. Thus, any change in tendon mechanical properties with aging may contribute to disability and loss of mobility of the elderly. Despite the importance of tendon to the function of the musculoskeletal system, the effects of age on tendon structure and function are incompletely understood. In addition, the responses of tendons in old animals to altered loading or biochemical environment and the mechanisms underlying the changes represent fundamental gaps in the field of musculoskeletal biology. Therefore, the goals of this dissertation were to (1) clarify how tendon structure and mechanics are altered with aging and (2) establish if age-associated changes can be delayed or reversed with exercise or the lifespan-extending drug Rapamycin. Using a novel technique of coupling regional mechanics and structural properties, we analyzed hindlimb tendons of adult (8-12 months) and old (28-30 months) mice. Tibialis anterior (TA) tendons stiffened with age, with the most pronounced increase in the region of the tendon nearest the muscle, where a 2-fold increase was observed. The mechanical changes in tendon were accompanied by suppressed collagen turnover and increased collagen crosslinking and calcification without changes in collagen fibril morphology. A similar degree of age-associated stiffening was observed for plantaris tendons, but 10 weeks of treadmill running, initiated at 27 months of age, essentially restored the adult phenotype in terms of mechanics and collagen turnover. Age-associated calcification of Achilles tendons was also partially abrogated following treadmill running. In contrast to reports from adult mice, the tendon extracellular matrix (ECM) remodeling was achieved without increased cell density or activation of tendon developmental pathways. Chronic administration of Rapamycin also impacted tendon properties, preventing the age-related changes in mechanical properties of TA tendons. This preservation of adult levels of tendon stiffness in old Rapamycin treated mice was accompanied by higher cell density than untreated old mice without changes in collagen synthesis. These findings demonstrate that mechanical and structural properties of mouse hindlimb tendons are altered in old age, but tendon maintains the ability to remodel its ECM, potentially through multiple mechanisms.