衰弱的分子机制与药物靶点研究进展

doi:10.3969/j.issn.1003-9198.2026.03.002

摘要/Abstract

摘要： 随着人口老龄化的加速,衰弱作为一种多因素驱动的综合征,已经成为老年医学与慢病管理领域的重要研究热点。衰弱的特征是力量、耐力及生理功能下降,可显著增加个体脆弱性、功能依赖和死亡风险。目前,推动其发生发展的生物学机制尚未被完全阐明,这在一定程度上限制了相关风险评估工具和干预策略的发展。近年来,多组学技术与生理、生化研究方法的快速进展,为系统解析衰弱的分子基础提供了新的研究路径。本文系统梳理了驱动衰弱的核心分子机制网络及药物靶点的最新研究进展,以期为未来衰弱机制研究与精准干预的转化提供参考。

关键词: 衰弱, 老年人, 慢性炎症, 药物靶点, 分子机制

Abstract: With the acceleration of population aging, frailty as a multifactorial medical syndrome has become an important research hotspot in geriatrics and chronic disease management. The features of fraitly are loss of strength, endurance and physiological function, which can significantly increase vulnerability, functional dependence and mortality risk. The biological mechanisms driving its occurrence and progression have not been fully elucidated, which to some extent limits the development of relevant risk assessment tools and intervention strategies. In recent years, the rapid progress of multi-omics technologies and physiological/biochemical research methods has provided new research pathways for systematically elucidating the molecular basis of frailty. This article systematically reviews the latest research progress on the core molecular mechanisms driving frailty and drug targets, providing a reference for future translational studies on frailty mechanisms and precision interventions.

Key words: frailty, aged, chronic inflammation, drug target, molecular mechanism

中图分类号:

R 592

刘钰坤, 雷佳炜, 朱春明, 张玉强, 王佳贺. 衰弱的分子机制与药物靶点研究进展[J]. 实用老年医学, 2026, 40(3): 224-228.

LIU Yukun, LEI Jiawei, ZHU Chunming, ZHANG Yuqiang, WANG Jiahe. Research progress on molecular mechanism and drug target of fraity syndrome[J]. Practical Geriatrics, 2026, 40(3): 224-228.

参考文献

[1] PERAZZA L R, BROWN-BORG H M, THOMPSON L V. Physiological systems in promoting frailty[J]Compr Physiol, 2022, 12(3): 3575-3620.
[2] ORLANDO FRAILTY CONFERENCE GROUP. Raising awareness on the urgent need to implement frailty into clinical practice[J]. J Frailty Aging, 2013, 2(3): 121-124.
[3] ROCKWOOD K, HOWLETT S E. Fifteen years of progress in understanding frailty and health in aging[J]. BMC Med, 2018, 16(1): 220.
[4] ŞAHBAT Y, GÜNER M, GÜRSOY S. Frailty: an overlooked red flag in sports surgery[J]. J Exp Orthop, 2025, 12(4): e70497.
[5] CALABRÒ A, ACCARDI G, AIELLO A, et al. Senotherapeutics to counteract senescent cells are prominent topics in the context of anti-ageing strategies[J]. Int J Mol Sci, 2024, 25(3): 1792.
[6] KIRKLAND J L, TCHKONIA T, ZHU Y, et al. The clinical potential of senolytic drugs[J]. J Am Geriatr Soc, 2017, 65(10): 2297-2301.
[7] LEE H, WILSON D, BUNTING K V, et al. Repurposing digoxin for geroprotection in patients with frailty and multimorbidity[J]. Ageing Res Rev, 2023, 86: 101860.
[8] SCHAFER M J, ZHANG X, KUMAR A, et al. The senescence-associated secretome as an indicator of age and medical risk[J]. JCI Insight, 2020, 5(12): e133668.
[9] FETARAYANI D, KAHDINA M, WAITUPU A, et al. Immunosenescence and the geriatric giants: molecular insights into aging and healthspan[J]. Med Sci: Basel, 2025, 13(3): 100.
[10] SCHULMAN I H, BALKAN W, HARE J M. Mesenchymal stem cell therapy for aging frailty[J]. Front Nutr, 2018, 5: 108.
[11] CLARK D, KOTRONIA E, RAMSAY S E. Frailty, aging, and periodontal disease: basic biologic considerations[J]. Periodontol 2000, 2021, 87(1): 143-156.
[12] LIGUORI I, RUSSO G, CURCIO F, et al. Oxidative stress, aging, and diseases[J]. Clin Interv Aging, 2018, 13: 757-772.
[13] PAUL J A, WHITTINGTON R A, BALDWIN M R. Critical illness and the frailty syndrome: mechanisms and potential therapeutic targets[J]. Anesth Analg, 2020, 130(6): 1545-1555.
[14] ERLANDSON K M, PIGGOTT D A. Frailty and HIV: moving from characterization to intervention[J]. Curr HIV/AIDS Rep, 2021, 18(3): 157-175.
[15] ZHU Y, TCHKONIA T, PIRTSKHALAVA T, et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs[J]. Aging Cell, 2015, 14(4): 644-658.
[16] LUÍS C, MADURO A T, PEREIRA P, et al. Nutritional senolytics and senomorphics: implications to immune cells metabolism and aging - from theory to practice[J]. Front Nutr, 2022, 9: 958563.
[17] PALLIYAGURU D L, MOATS J M, DI GERMANIO C, et al. Frailty index as a biomarker of lifespan and healthspan: focus on pharmacological interventions[J]. Mech Ageing Dev, 2019, 180: 42-48.
[18] ROSOFF D B, MAVROMATIS L A, BELL A S, et al. Multivariate genome-wide analysis of aging-related traits identifies novel loci and new drug targets for healthy aging[J]. Nat Aging, 2023, 3(8): 1020-1035.
[19] LORENZ E C, HICKSON L J, KHAIRALLAH P, et al. Cellular senescence and frailty in transplantation[J]. Curr Transplant Rep, 2023, 10(2): 51-59.
[20] KIRKLAND J L, TCHKONIA T. Senolytic drugs: from discovery to translation[J]. J Intern Med, 2020, 288(5): 518-536.
[21] BIELECKA-DABROWA A, EBNER N, DOS SANTOS M R, et al. Cachexia, muscle wasting, and frailty in cardiovascular disease[J]. Eur J Heart Fail, 2020, 22(12): 2314-2326.
[22] MAGGIO M, DE VITA F, LAURETANI F, et al. IGF-1, the cross road of the nutritional, inflammatory and hormonal pathways to frailty[J]. Nutrients, 2013, 5(10): 4184-4205.
[23] CAO Z, CHEN H, MIN J, et al. Proteomic landscape of multidimensional aging phenotypes[J]. Genome Med, 2025, 17(1): 122.
[24] MARCOZZI S, BIGOSSI G, GIULIANI M E, et al. Spreading senescent cells’ burden and emerging therapeutic targets for frailty[J]. Cells, 2023, 12(18): 2287.
[25] CASILE M, ALBRAND G, LAHAYE C, et al. Value of combining biological age with assessment of individual frailty to optimize management of cancer treated with targeted therapies: model of chronic myeloid leukemia treated with tyrosine kinase inhibitors (BIO-TIMER trial)[J]. BMC Cancer, 2024, 24(1): 661.
[26] WANG Q, ZHAO X, WANG W, et al. Identification of novel biomarkers and drug targets for frailty-related skeletal muscle aging: a multi-omics study[J]. QJM, 2025, 118(9): 657-677.
[27] SCASSELLATI C, CIANI M, GALOFORO A C, et al. Molecular mechanisms in cognitive frailty: potential therapeutic targets for oxygen-ozone treatment[J]. Mech Ageing Dev, 2020, 186: 111210.