Skeletal Muscle lipid and Insulin Resistance in Aging

衰老与骨骼肌能量代谢、胰岛素的变化有关 抵抗力和2型糖尿病(T2 DM)的高患病率。老龄化也是 与肌肉质量的进行性下降和肥胖症的增加有关，称为 骨质源性肥胖，导致行动不便和残疾。然而， 人类胰岛素抵抗和骨质疏松症的原因尚不清楚。这个项目将 提供有关潜在代谢因素的新信息 衰老肌肉中的功能障碍和骨骼肌减少--即线粒体和 心肌细胞内脂质的积聚。 在这个概念框架内，我们将帮助阐明 这两个重大的健康问题与老龄化有关。此外，我们还将提供 以干预为基础的证据以更好地了解这些复杂的年龄相关疾病 线粒体或心肌细胞内的脂质是否是改善的可修改目标 代谢和肌肉功能障碍的预防或治疗策略。 因此，我们的总体目标是在肌肉方面采用高度创新的方法 活检标本以确定功能和临床相关性 这些干预措施的后果以及几种新的生化变化 以及潜在的分子因素对人类骨骼的干预作用 肌肉。

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.