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

早期锻炼对肌腱成熟和晚年肌腱病抵抗力的影响

• 批准号: 10628956
• 负责人: Angela Horner
• 金额: $ 14.7万
• 依托单位: CALIFORNIA STATE UNIV SAN BERNARDINO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10628956
• 关键词: Address; Adolescent; Adult; Advanced Glycosylation End Products; Affect; Age; Aging; Area; Biological Assay; Cell Density; Cellular Structures; Collagen Fibril; Dimensions; Elderly; Exercise; Failure; Future; Growth; Harvest; Histology; Human; Isotopes; Label; Life; Locomotion; Lysine; Mechanics; Mitosis; Morphology; Mus; Musculoskeletal; Pathway interactions; Performance; Peripheral; Population; Preparation; Protocols documentation; Quality of life; Recording of previous events; Research; Resistance; Rodent; Role; Stress; Tendinopathy; Tendon Injuries; Tendon structure; Testing; Tissues; Training; age effect; age related; aged; aging population; cohort; exercise training; falls; healing; histological slides; improved; injured; mechanical load; mechanical properties; middle age; mouse model; protein degradation; repaired; response; sedentary; skeletal; stable isotope; tendon development

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.

项目概要 肌腱在运动中发挥着多种关键作用，功能可能会受到以下因素的影响： 衰老、废用和肌腱病对于老龄化人口来说，这些因素的结合大大减少了。 随年龄和/或训练而发生的许多结构变化。 肌腱中的变化已被证明会影响肌腱力学，包括横截面积（CSA）的变化， 运动可以拉直胶原纤维，并增加晚期糖基化终产物（AGE）。 减轻了一些与年龄相关的衰退，但之前的研究表明，肌腱的“核心” 完全由骨骼成熟形成，因此肌腱响应负荷的能力在成熟后受到限制 [16,17] 尽管存在这种现象，但早期肌腱对负荷的反应很大程度上是 未知，也不知道其对以后生活肌腱性能的影响。这项研究旨在解决两个问题。 理解个体发生与肌腱负荷相互作用的关键和相关差距——肌腱如何 早年的负荷会影响晚年的肌腱力学，以及早年肌腱对负荷的适应有何不同（如果 完全）来自成熟的肌腱，我们将测试早期生活锻炼预防晚年的潜力。 肌腱病并确定导致不同肌腱功能形态的结构机制 通过对小鼠进行 10 周的运动治疗，在幼年肌腱和成年肌腱之间进行比较 模型将在训练后立即收获肌腱并进行机械测试。 以及12个月后测试早期生命锻炼的能力，以增强晚年肌腱质量的形成。 将使用组织学和稳定同位素来分析肌腱核心的结构及其对生命早期负荷的反应， 从而捕捉肌腱在这些生命阶段对载荷的区域反应。