老年人肌少症治疗药物靶点的相关研究进展

doi:10.3969/j.issn.1003-9198.2026.03.003

摘要/Abstract

摘要： 肌少症是伴随人口老龄化加剧而普遍存在的进行性骨骼肌疾病,其特征为肌肉质量减少、力量下降及躯体功能减退,严重增加老年人群跌倒、失能及死亡风险。肌少症的发病机制错综复杂,涉及线粒体功能障碍、慢性炎症、蛋白质稳态失衡及神经肌肉接头退化等多重病理生理过程。目前,临床尚无获批的特异性治疗药物,主要依赖抗阻运动结合营养支持,但受限于患者依从性和个体差异,疗效难以保障。本文系统综述了肌少症的主要病理机制与现行药物治疗手段,并重点聚焦于具有研究价值的前沿治疗靶点,包括调节铁代谢以促进骨骼肌再生、靶向抑制肌抑素(Myostatin/ActRⅡB)信号通路、应用选择性雄激素受体调节剂(SARM)以及其他分子干预策略。本文旨在通过梳理最新研究进展,为开发精准、有效的肌少症治疗药物及综合干预方案提供理论依据与科学参考。

关键词: 肌少症, 老年人, 药物靶点, 信号通路

Abstract: Sarcopenia is a prevalent progressive skeletal muscle disease associated with aging population, which characterized by reduced muscle mass, decreased strength, and impaired physical function, significantly increasing the risk of falls, disability, and mortality in the elderly. The pathogenesis of sarcopenia is complex and involves multiple pathophysiological processes such as mitochondrial dysfunction, chronic inflammation, protein homeostasis imbalance, and neuromuscular junction degeneration. Currently, there are no approved specific therapeutic agents in clinical practice, and the treatment primarily relies on resistance training combined with nutritional support. However, due to the compliance and individual variability of patients, the efficacy is often difficult to ensure with certainty. This article provides a systematic review of the major pathological mechanisms and current therapeutic approaches for sarcopenia, with a focus on cutting-edge treatment targets of research value, including modulation of iron metabolism to promote skeletal muscle regeneration, targeted inhibition of the myostatin (Myostatin/ActRⅡB) signaling pathway, application of selective androgen receptor modulators (SARMs), and other molecular intervention strategies. This article aims to provide theoretical basis and scientific reference for the development of precise and effective therapeutic drugs and comprehensive intervention strategies for sarcopenia by reviewing the latest research progress.

Key words: sarcopenia, aged, drug target, signal pathway

中图分类号:

R 685

孙可欣, 雷佳炜, 张桂蕾, 杨镇溶, 王佳贺. 老年人肌少症治疗药物靶点的相关研究进展[J]. 实用老年医学, 2026, 40(3): 229-233.

SUN Kexin, LEI Jiawei, ZHANG Guilei, YANG Zhenrong, WANG Jiahe. Research progress on drug targets for the treatment of sarcopenia in the elderly[J]. Practical Geriatrics, 2026, 40(3): 229-233.

参考文献

[1] FANG E F, FANG Y, CHEN G, et al. Adapting health, economic and social policies to address population aging in China[J]. Nat Aging, 2025, 5(11): 2176-2187.
[2] CRUZ-JENTOFT A J, SAYER A A. Sarcopenia[J]. Lancet, 2019, 393(10191): 2636-2646.
[3] CRUZ-JENTOFT A J, BAHAT G, BAUER J, et al. Sarcopenia: revised European consensus on definition and diagnosis[J]. Age Ageing, 2019, 48(1): 16-31.
[4] CHEN L K, WOO J, ASSANTACHAI P, et al. Asian working group for sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment[J]. J Am Med Dir Assoc, 2020, 21(3): 300-307.e2.
[5] ZHANG X, LI H, HE M, et al. Immune system and sarcopenia: presented relationship and future perspective[J]. Exp Gerontol, 2022, 164: 111823.
[6] GIACOMELLO M, PYAKUREL A, GLYTSOU C, et al. The cell biology of mitochondrial membrane dynamics[J]. Nat Rev Mol Cell Biol, 2020, 21(4): 204-224.
[7] CHEN T H, KOH K Y, LIN K M, et al. Mitochondrial dysfunction as an underlying cause of skeletal muscle disorders[J]. Int J Mol Sci, 2022, 23(21): 12926.
[8] LIVSHITS G, KALINKOVICH A. Inflammaging as a common ground for the development and maintenance of sarcopenia, obesity, cardiomyopathy and dysbiosis[J]. Ageing Res Rev, 2019, 56: 100980.
[9] PAN L, XIE W, FU X, et al. Inflammation and sarcopenia: a focus on circulating inflammatory cytokines[J]. Exp Gerontol, 2021, 154: 111544.
[10] JIMENEZ-GUTIERREZ G E, MARTÍNEZ-GÓMEZ L E, MARTÍNEZ-ARMENTA C, et al. Molecular mechanisms of inflammation in sarcopenia: diagnosis and therapeutic update[J]. Cells, 2022, 11(15): 2359.
[11] MA K, FENG M, QIAO A, et al. Knockdown of CLEC4D alleviates myoblast dysfunction and inflammation in sarcopenia by inhibiting the JAK/STAT pathway[J]. BMC Musculoskelet Disord, 2025, 26(1): 981.
[12] NISHIKAWA H, FUKUNISHI S, ASAI A, et al. Pathophysiology and mechanisms of primary sarcopenia [J]. Int J Mol Med, 2021, 48(2).
[13] STUCK A K, BASILE G, FREYSTAETTER G, et al. Predictive validity of current sarcopenia definitions (EWGSOP2, SDOC, and AWGS2) for clinical outcomes: a scoping review[J]. J Cachexia Sarcopenia Muscle, 2023, 14(1): 71-83.
[14] PILLAY J, GAUDET L A, SABA S, et al. Falls prevention interventions for community-dwelling older adults: systematic review and meta-analysis of benefits, harms, and patient values and preferences[J]. Syst Rev, 2024, 13(1): 289.
[15] VINKE J S J, GORTER A R, EISENGA M F, et al. Iron deficiency is related to lower muscle mass in community-dwelling individuals and impairs myoblast proliferation[J]. J Cachexia Sarcopenia Muscle, 2023, 14(4): 1865-1879.
[16] FU W, LIU Y, YIN A, et al. Iron deficiency impairs muscle stem cell proliferation and skeletal muscle regeneration via HIF-2α stabilization[J]. J Cachexia Sarcopenia Muscle, 2025, 16(6): e70124.
[17] CHE Y, LI J, WANG P, et al. Iron deficiency-induced ferritinophagy impairs skeletal muscle regeneration through RNF20-mediated H2Bub1 modification[J]. Sci Adv, 2023, 9(46): eadf4345.
[18] ZHAO Y, XIA X, WANG Q, et al. Myostatin mutation enhances bovine myogenic differentiation through PI3K/AKT/mTOR signalling via removing DNA methylation of RACK1[J]. Cells, 2022, 12(1): 59.
[19] LESSARD S J, MACDONALD T L, PATHAK P, et al. JNK regulates muscle remodeling via myostatin/SMAD inhibition[J]. Nat Commun, 2018, 9(1): 3030.
[20] ABATI E, MANINI A, COMI G P, et al. Inhibition of myostatin and related signaling pathways for the treatment of muscle atrophy in motor neuron diseases[J]. Cell Mol Life Sci, 2022, 79(7): 374.
[21] LEE S J. Targeting the myostatin signaling pathway to treat muscle loss and metabolic dysfunction[J]. J Clin Invest, 2021, 131(9): e148372.
[22] PRIEGO T, MARTÍN A I, GONZÁLEZ-HEDSTRÖM D, et al. Role of hormones in sarcopenia[J]. Vitam Horm, 2021, 115: 535-570.
[23] DA FONSECA G W P, DWORATZEK E, EBNER N, et al. Selective androgen receptor modulators (SARMs) as pharmacological treatment for muscle wasting in ongoing clinical trials[J]. Expert Opin Investig Drugs, 2020, 29(8): 881-891.
[24] ROCH P J, WOLGAST V, GEBHARDT M M, et al. Combination of selective androgen and estrogen receptor modulators in orchiectomized rats[J]. J Endocrinol Invest, 2022, 45(8): 1555-1568.
[25] WEN J, SYED B, LEAPART J, et al. Selective androgen receptor modulators (SARMs) effects on physical performance: a systematic review of randomized control trials[J]. Clin Endocrinol, 2025, 102(1): 3-27.
[26] BAI G H, TSAI M C, TSAI H W, et al. Effects of branched-chain amino acid-rich supplementation on EWGSOP2 criteria for sarcopenia in older adults: a systematic review and meta-analysis[J]. Eur J Nutr, 2022, 61(2): 637-651.
[27] LI Y, LI C, ZHOU Q, et al. Multiomics and cellular senescence profiling of aging human skeletal muscle uncovers Maraviroc as a senotherapeutic approach for sarcopenia[J]. Nat Commun, 2025, 16(1): 6207.
[28] LUO X, ZHANG M, CHEN L, et al. Decorin deficiency promotes D-galactose-induced skeletal muscle atrophy and fibrosis by regulating ITGB1/Akt/mTOR signalling pathway[J]. J Cachexia Sarcopenia Muscle, 2025, 16(6): e70144.
[29] 刘艳慧, 朱哲, 何红丽, 等. 老年肌少症发病机制及中药防治老年肌少症机制的研究进展[J]. 中国老年学杂志, 2025, 45(15): 3814-3820.
[30] HUANG C Y, MAYER P K, WU M Y, et al. The effect of Tai Chi in elderly individuals with sarcopenia and frailty: a systematic review and meta-analysis of randomized controlled trials[J]. Ageing Res Rev, 2022, 82: 101747.