Early life exercise effects on tendon maturation and resistance to late life tendinopathies

项目摘要 肌腱在运动中起着多个关键作用，而功能可能会受到以下影响的影响 衰老、废用和肌腱病。对于老龄化的人口来说，这些因素的结合大大减少了 机动性和跌倒的可能性。随着年龄和/或训练而发生的许多结构性变化 肌腱中已被证明影响肌腱力学，包括横截面积(CSA)的变化， 胶原纤维拉直，晚期糖基化终末产物(AGEs)增加。锻炼可以 缓解一些与年龄相关的下降，但之前的研究表明，肌腱的“核心” 完全由骨骼成熟形成，因此肌腱对负荷的反应能力在成熟后是有限的 [16，17]。尽管有这种文献记载的现象，肌腱在生命早期对负荷的反应很大程度上是 未知，也不知道它对后世肌腱性能的影响。这项拟议的研究旨在解决两个问题 理解肌腱与肌腱负荷的个体发育相互作用的关键及相关差距--肌腱 早期生活中的负荷会影响后来的肌腱力学，以及早期生活中的肌腱对负荷的适应有何不同(如果 完全)来自成熟的肌腱。我们将测试早年锻炼预防晚年的潜力。 肌腱病变和识别导致不同肌腱功能形态的结构机制 在小鼠中使用10周运动治疗的幼年负重肌腱和成年负重肌腱之间的关系 模特。肌腱将在训练后立即采集并接受力学测试，因为 并在12个月后测试早期生活锻炼能力，提高晚年肌腱质量。队形 将使用组织学和稳定同位素来分析肌腱核心及其在早期生命中对负荷的反应， 从而捕捉到肌腱在这些生命阶段对负荷的区域反应。

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.