Project Summary Tendons serve multiple critical roles in locomotion, and functionality can be compromised by the effects of aging, disuse, and tendinopathy. For the aging population, the combination of these factors greatly reduces mobility and contributes to the likelihood of falling. Many structural changes that occur with age and/or training in tendon have been shown to impact tendon mechanics, including changes in cross-sectional area (CSA), straightening of collagen fibrils, and increase in advanced glycation end-products (AGEs). Exercise can mitigate some of these age-related declines, but previous studies have demonstrated that the ‘core’ of tendons is fully formed by skeletal maturity and thus the capacity of tendon to respond to load is limited post-maturation [16,17]. Despite this documented phenomenon, the response of tendon to loading in early life tendon is largely unknown, nor its consequences for later life tendon performance. This proposed research aims to address two key and related gaps in the understanding of ontogenetic interactions with tendon loading—how tendon loading in early life impacts later life tendon mechanics, and how early life tendon adaptation to load differs (if at all) from mature tendon. We will test the potential for early life exercise to protect against late-life tendinopathy and identify structural mechanisms contributing to differing tendon functional morphology between juvenile-loaded tendons and adult-loaded tendons using a 10-week exercise treatment in a mouse model. Tendons will be harvested and undergo mechanical testing both immediately following the training as well as 12 months later to test the ability of early life exercise to enhance late life tendon quality. The formation of the tendon core and its response to loading in early life will be assayed using histology and stable isotopes, thus capturing the regional response of tendon to loading at these life stages.