Skeletal Muscle lipid and Insulin Resistance in Aging

衰老与骨骼肌能量代谢、胰岛素的改变有关 耐药性和 2 型糖尿病 (T2DM) 患病率较高。衰老也是 与肌肉质量的逐渐丧失和肥胖增加有关，称为 肌肉减少性肥胖，导致活动受限和残疾。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 提供有关代谢潜在因素的新信息 衰老肌肉（即线粒体和肌肉减少症）的功能障碍和肌肉减少症 肌细胞内脂质的积累。 在这个概念框架内，我们将帮助阐明 这两个与衰老相关的重大健康问题。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与年龄相关的疾病 以及线粒体或肌细胞内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领域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型生化物质的改变 以及这些对人体骨骼的干预作用的潜在潜在分子因素 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.