MUSCLE PLASTICITY WITH RESISTANCE TRAINING AND DETRAINING IN OLDER ADULTS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项建议的总体目标是调查年龄对骨骼肌可塑性的影响，以应对渐进式阻力训练，维持阻力训练和停止训练。其目的不仅是表征年龄对训练适应性的短暂性的影响，而且还确定老年人维持渐进训练期间取得的临床重要收益所需的每周最低负荷量。这项建议的最初目的是检验一个假设，即随着渐进式阻力训练的进行，肌肉胰岛素样生长因子-I（IGF-I）的表达/可用性以及配体-受体结合下游的生肌/促有丝分裂作用将在两个年轻的（20-30岁）及以上（60-75岁）成年人，并将与第8周肌肉蛋白质合成净速率的类似相对增加相关，到第16周，肌纤维尺寸、大腿瘦体重和力量表现也有类似的相对增加。然而，人们认识到，年轻和老年肌肉之间的结构和生物学差异，包括肌纤维坏死，优先II型肌纤维萎缩，增加非收缩性组织，并在老年肌肉卫星细胞功能下降可能会影响变化的绝对幅度。我们期待类似的相对变化。这个建议的第二个目的是测试的假设，可逆性阻力训练适应停训期间发生更迅速地在老年男性和女性比年轻的科目。在停止训练16-32周后，老年受试者的肌纤维大小、大腿瘦体重、力量表现和负重运动难度预计将恢复到训练前的水平，但年轻受试者则不然。在年轻受试者中，更大的自发负重体力活动和更高的循环合成代谢激素基础水平预计与相对更高的停训抵抗力相关。在0、2、16和32周停止训练期间也将评估肌肉IGF-I系统组分，预计两个年龄组在第2周恢复至基线水平。虽然负荷敏感性局部IGF-I的表达和活性在负荷诱导的肥大过程中似乎比循环合成代谢激素更重要，但循环激素被认为在缺乏常规负荷方案的情况下对肌肉质量的组成性维持起主导作用。本提案的第三个目的是检验以下假设：维持训练适应性所需的每周最低抗阻运动量在老年人中比在年轻人中更大。减少初始渐进阻力训练量（3组x 3次练习x 3天/周）至1/3在16周的训练计划中使用的（3组x 3次练习x 1天/周）预计将保持年轻和老年受试者的训练适应性，但是将每周的训练量减少到初始训练计划的1/9（1组× 3次练习× 1天/周）预计仅能维持年轻受试者的训练适应性。 这一新的系列实验将：1）支持或反驳IGF-I在肌肉中的局部表达/可用性与机械负荷诱导的肌肉蛋白质合成和肌纤维大小的变化相关的假设; 2）回答在老年肌肉中阻力训练适应是否更短暂的临床重要问题;以及3）回答具有临床意义的问题，即减量训练对阻力训练适应性的维持是否受年龄的影响。 GCRC需要用于住院肌肉蛋白质周转研究（稳定同位素输注）和门诊抽血，激素/底物测定，人体测量学，饮食摄入分析，肌肉活检，以及（如果运动亚核心得到资助）运动测试，包括力量，功率，功能能力，有氧能力和运动难度。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this proposal is to investigate the impact of age on skeletal muscle plasticity in response to progressive resistance training, maintenance resistance training, and detraining. The purpose is not only to characterize the effect of age on the transient nature of training adaptations, but also to identify the minimum amount of weekly loading necessary for older adults to maintain clinically important gains achieved during progressive training. The initial aim of this proposal is to test the hypothesis that, consequent to progressive resistance training, expression/ availability of muscle insulin-like growth factor-I (IGF-I) and the myogenic/ mitogenic actions downstream from ligand-receptor binding will increase in both younger (20-30 years of age) and older (60-75 years of age) adults and will be associated with similar relative increases in the net rate of muscle protein synthesis by week 8, and similar relative increases in myofiber size, thigh lean mass, and strength performance by week 16. It is recognized, however, that structural and biological differences between young and older muscle including myofiber necrosis, preferential type II myofiber atrophy, increased noncontractile tissue, and decreased satellite cell function in older muscle may affect the absolute magnitudes of change. We expect similar relative changes. The second aim of this proposal is to test the hypothesis that reversibility of resistance training adaptations during detraining occurs more rapidly in older men and women than in young subjects. Myofiber size, thigh lean mass, strength performance, and weight-bearing exercise difficulty are expected to return to pretraining levels in older but not young subjects after 16-32 weeks of detraining. Greater spontaneous weight-bearing physical activity and higher basal levels of circulating anabolic hormones are expected to be associated with a relatively higher resistance to detraining in young subjects. Muscle IGF-I system components will also be assessed during detraining at 0, 2, 16, and 32 wk and are expected to return to baseline by wk 2 in both age groups. While load-sensitive local IGF-I expression and activity appear to be more important than circulating anabolic hormones during load-induced hypertrophy, circulating hormones are thought to play a dominant role toward constitutive maintenance of muscle mass in the absence of a regular loading regime. The third aim of this proposal is to test the hypothesis that the minimum weekly volume of resistance exercise required to maintain training adaptions is greater in older adults than in younger adults. Reducing the initial progressive resistance training volume (3 sets x 3 exercises x 3 d/wk) to 1/3 (3 sets x 3 exercises x 1 d/wk) of that employed during the 16-week training program is expected to maintain training adaptations in both young and older subjects, but reducing weekly volume to 1/9 (1 set x 3 exercises x 1 d/wk) of the initial program is expected to maintain training adaptations in young subjects only. This novel series of experiments will: 1) support or refute the hypothesis that local expression/availability of IGF-I in muscle is associated with mechanical load-induced changes in muscle protein synthesis and myofiber size; 2) answer the clinically significant question of whether or not resistance training adaptations are more transient in aged muscle; and 3) answer the clinically significant question of whether or not maintenance of resistance training adaptations with reduced-volume training is influenced by age. The GCRC is needed for inpatient muscle protein turnover studies (stable isotope infusions) and outpatient blood draws, hormone/substrate assays, anthropometrics, dietary intake anlysis, muscle biopsies, and (if the exercise subcore is funded) exercise testing including strength, power, functional capacity, aerobic power, and exercise difficulty.