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.

项目摘要 肌腱在运动中起着多个关键作用，功能可能会受到以下因素的影响 老化、废用和肌腱病。对于老龄化人口来说，这些因素的综合作用大大降低了 流动性，并有助于下降的可能性。随着年龄和/或训练而发生的许多结构变化 在钢筋束中已经显示出影响钢筋束力学，包括横截面积（CSA）的变化， 胶原纤维变直，以及晚期糖基化终产物（AGEs）增加。运动可以 减轻一些与年龄有关的下降，但以前的研究表明，肌腱的“核心”， 在骨骼成熟时完全形成，因此肌腱对负荷的反应能力在成熟后是有限的 [16，17]。尽管有这种记录的现象，但早期肌腱对载荷的反应在很大程度上是 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 理解个体发育与肌腱负荷相互作用的关键和相关差距 早期寿命中的载荷影响后期寿命肌腱力学，以及早期寿命肌腱对载荷的适应如何不同（如果 从成熟的肌腱。我们将测试早期生活锻炼的潜力，以防止晚年生活 肌腱病和鉴定导致不同肌腱功能形态结构机制 在小鼠中使用10周运动治疗的青少年负荷肌腱和成人负荷肌腱之间的关系 模型肌腱将在训练后立即收获并进行机械测试， 以及12个月后测试早期生活锻炼增强晚年生活肌腱质量的能力。形成 将使用组织学和稳定同位素来分析肌腱核心及其对早期负荷的反应， 从而捕获在这些寿命阶段钢筋束对载荷的区域响应。