Autophagy is an evolutionarily conserved, lysosome-dependent catabolic process whereby cytoplasmic components, including damaged organelles, protein aggregates and lipid droplets, are degraded and their components recycled. Autophagy has an essential role in maintaining cellular homeostasis in response to intracellular stress; however, the efficiency of autophagy declines with age and overnutrition can interfere with the autophagic process. Therefore, conditions such as sarcopenic obesity, insulin resistance and type 2 diabetes mellitus (T2DM) that are characterized by metabolic derangement and intracellular stresses (including oxidative stress, inflammation and endoplasmic reticulum stress) also involve the accumulation of damaged cellular components. These conditions are prevalent in ageing populations. For example, sarcopenia is an age-related loss of skeletal muscle mass and strength that is involved in the pathogenesis of both insulin resistance and T2DM, particularly in elderly people. Impairment of autophagy results in further aggravation of diabetes-related metabolic derangements in insulin target tissues, including the liver, skeletal muscle and adipose tissue, as well as in pancreatic β-cells. This Review summarizes the role of autophagy in the pathogenesis of metabolic diseases associated with or occurring in the context of ageing, including insulin resistance, T2DM and sarcopenic obesity, and describes its potential as a therapeutic target.

自噬是一种进化上保守的、依赖于溶酶体的分解代谢过程，细胞质成分（包括受损的细胞器、蛋白质聚集体和脂滴）被降解，其成分被回收。自噬在维持细胞稳态以应对细胞内应激方面起着至关重要的作用；然而，自噬的效率会随着年龄的增长而下降，营养过剩会干扰自噬过程。因此，以代谢紊乱和细胞内应激（包括氧化应激、炎症和内质网应激）为特征的肌肉减少性肥胖、胰岛素抵抗和 2 型糖尿病 (T2DM) 等病症也涉及受损细胞成分的积累。这些情况在老龄化人群中普遍存在。例如，肌肉减少症是一种与年龄相关的骨骼肌质量和强度损失，与胰岛素抵抗和 T2DM 的发病机制有关，尤其是在老年人中。自噬受损导致胰岛素靶组织（包括肝脏、骨骼肌和脂肪组织）以及胰腺 β 细胞中糖尿病相关代谢紊乱的进一步恶化。本综述总结了自噬在与衰老相关或在衰老背景下发生的代谢性疾病（包括胰岛素抵抗、T2DM 和肌肉减少性肥胖）发病机制中的作用，并描述了其作为治疗靶点的潜力。自噬受损导致胰岛素靶组织（包括肝脏、骨骼肌和脂肪组织）以及胰腺 β 细胞中糖尿病相关代谢紊乱的进一步恶化。本综述总结了自噬在与衰老相关或在衰老背景下发生的代谢性疾病（包括胰岛素抵抗、T2DM 和肌肉减少性肥胖）发病机制中的作用，并描述了其作为治疗靶点的潜力。自噬受损导致胰岛素靶组织（包括肝脏、骨骼肌和脂肪组织）以及胰腺 β 细胞中糖尿病相关代谢紊乱的进一步恶化。本综述总结了自噬在与衰老相关或在衰老背景下发生的代谢性疾病（包括胰岛素抵抗、T2DM 和肌肉减少性肥胖）发病机制中的作用，并描述了其作为治疗靶点的潜力。