Cyclic compressive loading as an intervention for skeletal muscle atrophy and imp

循环压缩负荷作为骨骼肌萎缩和小鬼的干预措施

• 批准号: 8666702
• 负责人: Timothy Alan Butterfield
• 金额: $ 18.75万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8666702
• 关键词: Activities of Daily Living; Address; Age; Age-Months; Aging; Animals; Atrophic; Attenuated; Cells; Cellular Infiltration; Clinical; Data; Dependence; Development; Disease; Elderly; Energy Metabolism; Exercise; Exhibits; Frequencies; Gastrocnemius Muscle; Goals; Hindlimb; Immune; Immune response; Infiltration; Inflammatory; Inflammatory Response; Injury; Intervention; Leg; Limb structure; Maintenance; Massage; Measures; Modeling; Muscle; Muscle Proteins; Muscle function; Muscular Atrophy; NIH Program Announcements; Natural regeneration; Necrosis; Operative Surgical Procedures; Pathway interactions; Predisposition; Preventive Intervention; Process; Protein Biosynthesis; Proteins; Rattus; Rattus norvegicus; Recovery; Research; Signal Pathway; Skeletal Muscle; Suspension substance; Suspensions; Testing; Time; Translating; age related; aged; clinical practice; frailty; improved; juvenile animal; male; mortality; muscle form; muscle strength; novel; prevent; protein degradation; public health relevance; repaired; research study; response; restoration; sarcopenia; therapy design

DESCRIPTION (provided by applicant): Aging is associated with a decreased ability to recover muscle mass and strength after periods of inactivity, to which elderly are often subjected, resulting in frailty and functional dependence. Skeletal muscle is not only critically important for the development of force, but also serves as a major protein reservoir and is an important predictor of mobility, susceptibility to injury, and mortality. Therefore, it is criticaly important to design interventions to attenuate the decrease in muscle size during periods of disuse and to aid in the regrowth of atrophied muscle. Underlying mechanisms for the diminished capacity of muscle to regrow after disuse in the elderly are still largely unknown, but could be related to alterations in the inflammatory processes associated with recovery from atrophy. Massage therapy is used in clinical settings to aid in the repair of inflammatory conditions in muscles and we have found that massage in the form of cyclic compressive loading (CCL) positively modulates the immune response in muscle and aids in the repair of muscle injury and restoration of function in young animals. However, the effect of massage therapy on muscle atrophy and regrowth in the aged is completely unexplored. Therefore, we hypothesize that CCL is beneficial for the maintenance of muscle size during disuse-induced atrophy and will improve the impaired regrowth response in aged rats. We will investigate this hypothesis with two specific aims. In Aim 1 we hypothesize that CLL attenuates muscle mass lost during disuse-induced atrophy through actions on protein turnover pathways. Male Fischer 344/Brown Norway rats at 10 and 30 months of age will be hind limb suspended for 14 days to induce atrophy. CCL will be applied at two different loads in different groups of rats to gastrocnemius muscles of one leg during hind limb suspension. Changes in muscle size protein synthesis, markers of muscle protein synthesis and degradation, and force generating capacity will be measured. In Aim 2 we hypothesize that CCL will improve regrowth of muscle in aged rats through its immunomodulatory actions. Rats at 10 and 30 months of age will be hindlimb suspended for 14 days followed by ambulation for 1, 2, 4 or 14 days. CCL will be applied at two different loads to gastrocnemius muscle of one leg starting immediately after reambulation to assess the effect of CCL on recovery of muscle size after atrophy. Muscles will be assessed for size, immune cell infiltration, degradation and regeneration, and protein synthesis and degradation markers, as well as force generating capacity. The experiments proposed in this application will indicate whether massage therapy is beneficial for muscle maintenance in general and muscle size and strength restoration in the aged in particular. The age- associated diminished capacity to recover muscle mass lost during disuse is of great clinical importance and it is critically important to develop strategies that can prevent inactivity-induced atrophy or aid in the recovery of muscle mass lost during disuse. If our results prove beneficial, massage can be directly applied clinically for the maintenance and restoration of muscle size and strength.

描述(申请人提供)：衰老与在一段时间不活动后恢复肌肉质量和力量的能力降低有关，这是老年人经常受到的影响，导致虚弱和功能依赖。骨骼肌不仅对力量的发育至关重要，而且是主要的蛋白质储存库，是运动能力、损伤易感性和死亡率的重要预测指标。因此，重要的是设计干预措施，以减缓在停用期间肌肉大小的减少，并帮助萎缩肌肉的再生。老年人停用后肌肉再生能力减弱的潜在机制仍在很大程度上尚不清楚，但可能与与萎缩恢复相关的炎症过程的改变有关。在临床环境中，按摩疗法被用来帮助修复肌肉中的炎症状态，我们发现以循环压缩负荷(CCL)形式的按摩可以积极地调节肌肉中的免疫反应，并有助于修复肌肉损伤和恢复幼年动物的功能。然而，推拿疗法对老年人肌肉萎缩和再生的影响还完全没有被探索。因此，我们假设CCL在废用诱导的萎缩期间有利于维持肌肉的大小，并将改善老年大鼠受损的再生反应。我们将以两个具体目标来研究这一假说。在目标1中，我们假设CLL通过对蛋白质周转途径的作用来减少在废用诱导的萎缩过程中失去的肌肉质量。将10和30月龄雄性Fischer 344/Brown挪威大鼠的后肢悬吊14天，以诱导萎缩。在后肢悬吊过程中，对不同组大鼠一侧腓肠肌分别施加两种不同负荷的CCL。将测量肌肉大小、蛋白质合成、肌肉蛋白质合成和降解的标志物以及力量产生能力的变化。在目标2中，我们假设CCL通过其免疫调节作用促进老龄大鼠肌肉的再生。10月龄和30月龄大鼠后肢悬吊14天，然后步行1、2、4或14天。术后立即对一侧小腿腓肠肌施加两种不同负荷的CCL，以评价CCL对萎缩后肌肉大小恢复的影响。将评估肌肉的大小、免疫细胞渗透、降解和再生、蛋白质合成和降解标记物以及力量产生能力。本申请中提出的实验将表明按摩疗法是否有利于总体上的肌肉维持，特别是对老年人的肌肉大小和力量的恢复。与年龄相关的恢复在停用过程中失去的肌肉质量的能力减弱具有重要的临床意义，开发能够防止不活动引起的萎缩或 帮助恢复在停用时失去的肌肉质量。如果我们的结果被证明是有益的，按摩可以直接应用于临床，以维持和恢复肌肉的大小和力量。