Use of insulin sensitizers to offset skeletal muscle dysfunction during immobility

摘要 老年人因疾病、损伤和/或手术住院可能会损害身体活动能力， 因此，老年人在住院期间和以后都有能力进行身体活动。所得 久坐不动的生活方式可能会被接受为新的常态，最终增加骨骼肌的风险 功能障碍（例如肌肉减少症）。 肌肉萎缩和力量损失是老年人废用的不幸后果。我们有 通过我们对健康老年人的卧床休息研究观察到，除了肌肉和力量的变化， 骨骼肌炎症显著增加，与去甲肾上腺素相关的酶上调， 神经酰胺新生物合成。局部炎症和神经酰胺（一种有毒脂质中间体）的积累， 会阻碍肌肉生长二甲双胍治疗可以通过钝化炎症通路来减轻肌肉损失 和神经酰胺积累。虽然二甲双胍传统上用作胰岛素增敏剂，但其作为胰岛素增敏剂的用途是非常广泛的。 在老年人身体不活动期间保持肌肉健康的预防策略尚未得到 研究了 因此，我们建议在老年人中进行临床研究，以测试二甲双胍治疗是否 在卧床休息期间将减弱肌肉萎缩、虚弱和肌肉炎症机制。这些 这些发现将为开发新的治疗方法奠定基础，如二甲双胍，以防止肌肉萎缩。 老年人在废用期的功能障碍。

Abstract Hospitalizations for disease, injury, and/or surgery in older adults are likely to impair physical mobility and, therefore, the older adults capacity to be physically active both during hospitalization and beyond. The resulting sedentary lifestyle is likely to be accepted as the new normal, ultimately increasing the risk of skeletal muscle dysfunction (e.g. sarcopenia). Muscle atrophy and loss in strength is an unfortunate consequence with disuse in older adults. We have observed with our bed rest studies in healthy older adults that in addition to muscle and strength changes, there is a substantial increase in skeletal muscle inflammation and an upregulation of enzymes related to de novo ceramide biosynthesis. The accumulation of local inflammation and ceramide, a toxic lipid intermediate, can impair muscle growth. Metformin treatment may attenuate muscle loss by blunting inflammatory pathways and ceramide accumulation. Though metformin has traditionally served as an insulin sensitizer, its use as a preventive strategy to maintain muscle health during a period of physical inactivity in older adults has not been investigated. Therefore, we have proposed to conduct a clinical study in older adults to test whether metformin treatment during bed rest will attenuate muscle atrophy, weakness and muscle inflammatory mechanisms. These findings will be foundational in the development of novel treatments, such as metformin, to prevent muscle dysfunction in older adults during disuse periods.!