MUSCLE PLASTICITY WITH RESISTANCE TRAINING AND DETRAINING IN OLDER ADULTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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、维持阻力训练和解除训练。其目的不仅是为了刻画年龄对训练适应的暂时性的影响，而且也是为了确定老年人保持在渐进训练中取得的临床重要成果所需的每周最低负荷量。这项建议的最初目的是检验这样一种假设：由于渐进式阻力训练，年轻人(20-30岁)和老年人(60-75岁)的肌肉胰岛素样生长因子-I(IGF-I)的表达/可获得性以及配体-受体结合下游的生肌/有丝分裂作用都将增加，并将与第8周时肌肉蛋白质合成净速率的类似相对增加以及第16周时肌纤维大小、大腿瘦肉质量和力量表现的类似相对增加有关。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，老年肌肉中优先的II型肌纤维萎缩、非收缩组织增多和卫星细胞功能降低可能会影响变化的绝对程度。我们预计会出现类似的相对变化。这项建议的第二个目的是检验这样一种假设，即在解除训练期间，阻力训练适应的可逆性在老年男性和女性中比在年轻受试者中发生得更快。在16-32周的减训后，年龄较大但不年轻的受试者的肌纤维大小、大腿瘦肉质量、力量表现和负重运动难度预计将恢复到训练前的水平。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脱训抵抗力有关。肌肉IGF-I系统成分也将在0、2、16和32wk的去训练过程中进行评估，并预计在两个年龄组的wk2恢复到基线。在负荷诱导的肥大过程中，负荷敏感的局部IGF-I的表达和活性似乎比循环合成激素更重要，但循环激素被认为在缺乏规则负荷机制的情况下对肌肉质量的结构性维持起主导作用。这项建议的第三个目的是检验这样一个假设，即维持训练适应所需的每周最小阻力运动量在老年人中比年轻人更大。将最初的递增阻力训练量(3套×3个练习×3d/周)减少到16周训练期间的1/3(3套×3个练习×1d/wk)，预计将维持年轻和老年受试者的训练适应能力，但将每周训练量减少到初始计划的1/9(1套×3个练习×1d/wk)，仅有望维持年轻受试者的训练适应能力。 这一系列新颖的实验将：1)支持或驳斥肌肉中IGF-I的局部表达/可获得性与机械负荷引起的肌肉蛋白质合成和肌纤维大小变化有关的假设；2)回答抵抗训练适应在老年肌肉中是否更短暂的临床意义问题；以及3)回答年龄是否影响减量训练维持阻力训练适应的临床意义问题。 GCRC用于住院患者肌肉蛋白质周转研究(稳定同位素输注)和门诊抽血、激素/底物分析、人体测量学、饮食摄入量分析、肌肉活组织检查，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、有氧功率和运动难度。

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.