Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Institute of Brain Science and Brain-inspired Technology of West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Neurology, Chengdu Shangjin Nanfu Hospital, Chengdu, Sichuan, China.
Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Institute of Brain Science and Brain-inspired Technology of West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Neurology, Chengdu Shangjin Nanfu Hospital, Chengdu, Sichuan, China.
Metabolism. 2024 Nov;160:155998. doi: 10.1016/j.metabol.2024.155998. Epub 2024 Aug 10.
Sarcopenia is a geriatric syndrome characterized by a functional decline in muscle. The prevalence of sarcopenia increases with natural aging, becoming a serious health problem among elderly individuals. Therefore, understanding the pathology of sarcopenia is critical for inhibiting age-related alterations and promoting health and longevity in elderly individuals. The development of sarcopenia may be influenced by interactions between visceral and subcutaneous adipose tissue and skeletal muscle, particularly under conditions of chronic low-grade inflammation and metabolic dysfunction. This hypothesis is supported by the following observations: (i) accumulation of senescent cells in both adipose tissue and skeletal muscle with age; (ii) gut dysbiosis, characterized by an imbalance in gut microbial communities as the main trigger for inflammation, sarcopenia, and aged adipose tissue; and (iii) microbial dysbiosis, which could impact the onset or progression of a senescent state. Moreover, adipose tissue acts as an endocrine organ, releasing molecules that participate in intricate communication networks between organs. Our discussion focuses on novel adipokines and their role in regulating adipose tissue and muscle, particularly those influenced by aging and obesity, emphasizing their contributions to disease development. On the basis of these findings, we propose that age-related adipose tissue and sarcopenia are disorders characterized by chronic inflammation and metabolic dysregulation. Finally, we explore new potential therapeutic strategies involving specialized proresolving mediator (SPM) G protein-coupled receptor (GPCR) agonists, non-SPM GPCR agonists, transient receptor potential (TRP) channels, antidiabetic drugs in conjunction with probiotics and prebiotics, and compounds designed to target senescent cells and mitigate their pro-inflammatory activity.
肌肉减少症是一种以肌肉功能下降为特征的老年综合征。随着自然衰老，肌肉减少症的患病率增加，成为老年人的严重健康问题。因此，了解肌肉减少症的发病机制对于抑制与年龄相关的改变、促进老年人的健康和长寿至关重要。肌肉减少症的发展可能受到内脏和皮下脂肪组织与骨骼肌之间相互作用的影响，特别是在慢性低度炎症和代谢功能障碍的情况下。以下观察结果支持这一假说：（i）随着年龄的增长，脂肪组织和骨骼肌中衰老细胞的积累；（ii）肠道菌群失调，以肠道微生物群落失衡为主要炎症、肌肉减少症和衰老脂肪组织的触发因素；以及（iii）微生物失调，可能影响衰老状态的发生或进展。此外，脂肪组织作为内分泌器官，释放参与器官间复杂通讯网络的分子。我们的讨论集中在新型脂肪因子及其在调节脂肪组织和肌肉中的作用上，特别是受衰老和肥胖影响的脂肪因子和肌肉，强调它们对疾病发展的贡献。基于这些发现，我们提出与年龄相关的脂肪组织和肌肉减少症是慢性炎症和代谢失调为特征的疾病。最后，我们探讨了涉及特异性解决介质（SPM）G 蛋白偶联受体（GPCR）激动剂、非 SPM GPCR 激动剂、瞬时受体电位（TRP）通道、与益生菌和益生元联合使用的抗糖尿病药物以及旨在靶向衰老细胞并减轻其促炎活性的化合物等新的潜在治疗策略。
