Impact of Exercise on Sarcopenia

运动对肌肉减少症的影响

基本信息

批准号：
8471032
负责人：
JUDD M. AIKEN
金额：
$ 37.31万
依托单位：
UNIVERSITY OF ALBERTA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-15 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8471032
关键词：
Aerobic Aerobic Exercise Affect Age Age-Months Aging Animals Apoptotic Area Atrophic Attenuated Benefits and Risks Biological Models Complex Contractile Proteins Contralateral Cytochrome c Reductase Data Deletion Mutation Elderly Electron Transport Etiology Event Exercise Exhibits Fiber Genome Genotype Goals Health Human Hybrids Infiltration Intervention Link Literature Mammals Mechanics Mitochondria Mitochondrial DNA Modeling Moderate Exercise Molecular Morphology Muscle Muscle Fibers Muscle function Mutation Necrosis Norway Outcome Study Oxidases Phenotype Play Prevalence Process Property Rattus Regimen Role Skeletal Muscle Soleus Muscle Succinate Dehydrogenase System Testing Time Training age related aged base combat cytochrome c oxidase design disability enzyme activity healthy aging male mature animal mitochondrial DNA mutation muscle aging muscle form rectus femoris research study sarcopenia sedentary tool vastus lateralis

项目摘要

Sarcopenia, the loss of muscle mass and function due to muscle fiber loss and atrophy, is a prominent and debilitating age-related consequence in humans. There is a need for a healthy aging model system to efficiently evaluate potential interventions that delay or reduce sarcopenia of the aged. We defined the onset of significant muscle mass and fiber loss in the Fischer 344 x Brown Norway hybrid rat (FBN) at 30 months of age. Our studies have demonstrated that mitochondrial DNA (mtDNA) abnormalities play a causal role in muscle fiber loss. We have shown that age-dependent mtDNA deletion mutations clonally accumulate to high levels in aged skeletal muscle fibers. Concomitant with this increase in aberrant genomes is a loss of complex IV (cytochrome c oxidase; COX-) activity of the electron transport system (ETS) and the hyper-reactivity of complex II (succinate dehydrogenase; SDH++). These COX-/SDH++ regions of abnormal fibers are prone to atrophy and breakage, linking a molecular event, mtDNA deletion mutations, with an aging phenotype, muscle fiber loss. Endurance training is a common intervention employed by the elderly to combat the loss of muscle mass and function that occurs with age. Very little, however, is known of the impact of this intervention in very old humans or animals. We have recently completed a study showing that 3 months of high intensity endurance training, initiated at 30 months of age in the male FBN rat, increased the prevalence of ETS abnormal fibers, a detrimental process that leads to fiber loss. Our data is consistent with a rapidly growing body of literature that indicates the level of exercise necessary for beneficial adaptation declines with age. We hypothesize that the benefits/risks of aerobic exercise is dependent on i) the age at which aerobic exercise is initiated and ii) the intensity level of the exercise. To test this hypothesis, we will initiate two levels of exercise (moderate and high) prior to (24-month-old rats; SA1) and at the onset (30-month-old rats; SA2) of significant accumulation of mitochondrial abnormalities, muscle mass loss and fiber loss in male FBN rats. The sarcopenic profiles (muscle morphology and fiber fate) will be determined in control rats (sedentary at 24-. 30 and 36 months) and experimental rats at 36-months of age. These analyses will define muscle mass, muscle cross-sectional area, fiber number, fiber cross-sectional area, fiber type and fibrotic infiltration, as well as the number of fibers exhibiting necrotic and apoptotic changes. The impact of exercise on the abundance and progression and mtDNA deletion load will be determined in affected fibers (SA 3). We will also ascertain if single fibers with high mtDNA deletion loads have altered contractile function and whether exercise alters the mechanical properties of affected single fibers (SA4). This exercise model will serve as a means of testing our proposed mechanism of age-related fiber loss as well as further our understanding of the impact of aerobic exercise in aged skeletal muscle. An important outcome of these studies is to determine if endurance training, a commonly employed intervention of sarcopenia, can be beneficial to muscle health in old mammals. 1

肌肉减少症，即由于肌纤维损失和萎缩而导致的肌肉质量和功能丧失，是一种突出且常见的疾病。对人类造成与年龄相关的衰弱后果。需要一个健康老龄化模型系统有效评估延迟或减少老年人肌肉减少症的潜在干预措施。我们定义了起始点 Fischer 344 x 挪威棕色杂交大鼠 (FBN) 在 30 个月时出现显着的肌肉质量和纤维损失年龄。我们的研究表明线粒体 DNA (mtDNA) 异常在肌纤维损失。我们已经证明，年龄依赖性 mtDNA 缺失突变可克隆地积累到高水平老化骨骼肌纤维的水平。与异常基因组的增加相伴的是复杂基因组的丧失。 IV（细胞色素 c 氧化酶；COX-）电子传递系统 (ETS) 的活性以及复合物 II（琥珀酸脱氢酶；SDH++）。这些异常纤维的 COX-/SDH++ 区域容易发生萎缩和断裂，将分子事件、mtDNA 缺失突变与衰老表型、肌肉联系起来纤维损失。耐力训练是老年人用来对抗肌肉损失的常见干预措施随着年龄的增长而出现的质量和功能。然而，人们对这种干预措施的影响知之甚少。老人类或动物。我们最近完成的一项研究表明，3 个月的高强度训练雄性 FBN 大鼠 30 月龄时开始的耐力训练增加了 ETS 的患病率异常纤维，一种导致纤维损失的有害过程。我们的数据与快速增长的市场是一致的大量文献表明，有益适应所需的运动水平随着年龄的增长而下降。我们假设有氧运动的益处/风险取决于 i) 有氧运动的年龄开始和 ii) 锻炼的强度水平。为了检验这个假设，我们将启动两个级别的锻炼（中度和高）之前（24 个月大的大鼠；SA1）和开始时（30 个月大的大鼠；SA2）雄性 FBN 大鼠线粒体异常积累、肌肉质量损失和纤维损失。这肌肉减少特征（肌肉形态和纤维命运）将在对照大鼠（24-30 久坐）中测定和36个月）和36个月大的实验大鼠。这些分析将定义肌肉质量、肌肉横截面积、纤维数量、纤维横截面积、纤维类型和纤维化浸润，以及表现出坏死和凋亡变化的纤维数量。运动对丰度的影响将在受影响的纤维中确定进展和 mtDNA 缺失负荷 (SA 3)。我们还将确定是否具有高 mtDNA 缺失负荷的单纤维改变了收缩功能，运动是否会改变收缩功能受影响的单纤维的机械性能（SA4）。这个练习模型将作为测试我们的方法提出了与年龄相关的纤维损失的机制，并进一步了解了有氧运动的影响锻炼老年骨骼肌。这些研究的一个重要成果是确定耐力训练是否肌肉减少症的常用干预措施可能有益于老年哺乳动物的肌肉健康。 1

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effect of age and exercise on the viscoelastic properties of rat tail tendon.

DOI：
10.1007/s10439-013-0796-4
发表时间：
2013-06
期刊：
ANNALS OF BIOMEDICAL ENGINEERING
影响因子：
3.8
作者：
LaCroix, Andrew S.;Duenwald-Kuehl, Sarah E.;Brickson, Stacey;Akins, Tiffany L.;Diffee, Gary;Aiken, Judd;Vanderby, Ray, Jr.;Lakes, Roderic S.
通讯作者：
Lakes, Roderic S.

Effect of aging on power output properties in rat skinned cardiac myocytes.

衰老对大鼠皮心肌细胞功率输出特性的影响。

DOI：
10.1093/gerona/glr150
发表时间：
2011
期刊：
The journals of gerontology. Series A, Biological sciences and medical sciences
影响因子：
0
作者：
Chung,Eunhee;Diffee,GaryM
通讯作者：
Diffee,GaryM

Apoptosis and necrosis mediate skeletal muscle fiber loss in age-induced mitochondrial enzymatic abnormalities.