Skeletal Muscle lipid and Insulin Resistance in Aging

描述（由申请方提供）：衰老与骨骼肌能量代谢、胰岛素抵抗和2型糖尿病（T2 DM）患病率升高相关。衰老还与肌肉质量的进行性损失和增加的肥胖有关，称为肌肉减少性肥胖，这导致移动性限制和残疾。然而，人类胰岛素抵抗和肌肉减少症的原因尚不清楚。该项目将提供有关衰老肌肉中代谢功能障碍和肌减少症的潜在因素的新信息-即线粒体和肌细胞内脂质的积累。在这个概念框架内，我们将帮助阐明这两个重要的健康问题与老龄化的生物学基础。此外，我们将提供基于干预的证据，以更好地了解这些复杂的年龄相关疾病，以及线粒体或肌细胞内脂质是否是改善代谢和肌肉功能障碍预防或治疗策略的可修改目标。因此，我们的总体目标是在肌肉活检标本中采用高度创新的方法，以确定这些干预措施的功能和临床相关后果，以及可能导致这些干预措施对人类骨骼肌影响的几种新型生化和分子因素的改变。 公共卫生相关性：节食减肥可能对老年人，超重的男性和女性有积极的好处。然而，这些好处可能是以肌肉组织损失为代价的。该项目将提供人类骨骼肌中独特的生化和分子靶点，这些靶点是老年男性和女性节食减肥的益处以及潜在的负面后果的基础。

DESCRIPTION (provided by applicant): Aging is associated with alterations in skeletal muscle energy metabolism, insulin resistance and a higher prevalence of type 2 diabetes mellitus (T2DM). Aging is also associated with a progressive loss of muscle mass and increased adiposity, known as sarcopenic obesity, which leads to mobility limitations and disability. However, the causes of insulin resistance and sarcopenia in humans are not known. This project will provide novel information regarding potential factors underlying both metabolic dysfunction and sarcopenia in aging muscle - namely, mitochondria and the accumulation of intramyocellular lipids. Within this conceptual framework we will help elucidate the biological underpinnings of these two significant health problems related to aging. In addition, we will provide intervention-based evidence to better understand these complex age-related disorders and whether mitochondria or intramyocellular lipids are modifiable targets for improved prevention or treatment strategies for metabolic and muscle dysfunction. Therefore, our overall objectives are to employ highly innovative methods in muscle biopsy specimens in order to determine the functional and clinically relevant consequences of these interventions as well as alterations in several novel biochemical and molecular factors potentially underlying these intervention effects on human skeletal muscle. PUBLIC HEALTH RELEVANCE: Dieting to lose weight may have positive benefits in older, overweight men and women. However, these benefits may come at a cost regarding the loss of muscle tissue. This project will provide unique biochemical and molecular targets in human skeletal muscle underlying the benefits as well as the potential negative consequences of dieting to lose weight in older men and women.