老年衰弱与肌少症 (1).pdf

海南医学2023年8月第34卷第15期Hainan Med J,Aug.2023,Vol.34,No.15老年衰弱与肌少症唐鑫钰，黄贤涛，马曌 综述杨帆 审校遵义医科大学第三附属医院&遵义市第一人民医院，贵州遵义563000【摘要】衰弱涉及多器官系统的生物储备丧失、平衡失调，在轻微应激事件后易发生生理失代偿，可增加老年人对不良事件的易感性；肌少症是低肌肉质量与肌肉功能的组合，与年龄相关，并对老年人的日常生活质量造成很大影响。肌少症同时也是衰弱评估中的组成部分。随着人口老龄化的加速到来，衰弱人数与日俱增，而肌少症作为其表现之一也逐步进入公众的视线。本文就衰弱和肌少症的发生机制、流行病学、诊断、干预措施等方面的研究进展做一综述，为探究两者机制关系及早期干预等方面提供借鉴。【关键词】老年；衰弱；肌少症；关联；综述【中图分类号】R339.3+8【文献标识码】A【文章编号】10036350（2023）15227205Association between elderly frailty and sarcopenia.TANG Xin-yu,HUANG Xian-tao,MA Zhao,YANG Fan.The ThirdAffiliated Hospital of Zunyi Medical University&The First Peoples Hospital of Zunyi,Zunyi 563000,Guizhou,CHINA【Abstract】Frailty involves loss of biological reserves and imbalance of multiple organ systems and is prone tophysiological decompensation after mild stress events,which can increase the susceptibility of the elderly to adverseevents.Sarcopenia,which refers to the combination of low muscle mass and muscle function,is age-related and has agreat impact on the quality of daily life of the elderly.Sarcopenia is also part of the frailty assessment.With the accelera-tion of the aging of the population,the number of frailty is increasing,and as one of its manifestations,sarcopenia isgradually coming into the public eye.This paper reviews the research progress of the mechanism,epidemiology,diagno-sis,and intervention measures of frailty and sarcopenia,so as to provide reference for exploring the mechanism relation-ship and early intervention of frailty and sarcopenia.【Key words】Elderly;Frailty;Sarcopenia;Association;Review 综述 doi:10.3969/j.issn.1003-6350.2023.15.033基金项目：贵州省卫生健康委科学技术基金项目(编号：gzwjkj2020-1-022)。第一作者：唐鑫钰(1998)，女，硕士，住院医师，主要研究方向：衰弱及肌少症的发病机理与进展。通讯作者：杨帆(1968)，女，博士，主任医师，硕士生导师，主要研究方向：衰弱的发病机理与进展，E-mail：。伴随全球老龄化形势加剧，衰弱和肌少症逐渐成为老年失能领域的热点话题。衰弱与肌少症临床表现相似，且患病率与年龄相关，却又各具特点，且均对老年人生活及生命质量产生影响。因此，对比衰弱与肌少症的定义，找寻两者临床表现、发病机制之间的联系,可为衰弱和肌少症的预防提供借鉴及指导。1定义衰弱(frailty)是与年龄相关的临床综合征，表现为老年人生理储备能力下降导致易损性增加、抗应激能力减退的非特异性状态；即使轻微刺激，衰弱老人都marker expression correlated with 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vulnerable phenotype J.J Stroke,2021,23(3):367-376.29 Tony AA,Tony EA,Mohammed WS,et al.Evaluation of plasma lev-els of neopterin and soluble CD40 ligand in patients with acute isch-emic stroke in upper Egypt:Can they surrogate the severity and func-tional outcome?J.Neuropsychiatr Dis Treat,2019,15:575-586.30 Seijkens TTP,Van Tiel CM,Kusters PJH,et al.Targeting CD40-in-duced TRAF6 signaling in macrophages reduces atherosclerosis J.JAm Coll Cardiol,2018,71(5):527-542.31 Ots HD,Tracz JA,Vinokuroff KE,et al.CD40-CD40L in neurologi-cal disease J.Int J Mol Sci,2022,23(8):4115.(收稿日期：2023-02-07)2272Hainan Med J,Aug.2023,Vol.34,No.15海南医学2023年8月第34卷第15期可能出现一系列负性临床事件，如非计划性入院、住院时间延长、失能、死亡等1。同样地，在正常老化过程中，骨骼肌质量在30岁左右时达到峰值，之后，随着年龄的增加，每年约有1%的肌量丢失，50岁以后每年下降1.5%，在70岁之后这个过程会更快，每年下降约3%2。肌少症(sarcopenia)主要表现为渐进性和全身性肌肉质量减少和功能减退，并伴有生活质量下降和死亡率增加等不良风险，其与活动障碍、跌倒、低骨密度及代谢紊乱密切相关，是老年人生理功能逐渐减退的重要原因和表现之一3-4。从定义上看，衰弱与肌少症存在部分重叠，与年龄相关，且都表现为机体力量及耐力下降并增加不良事件的发生率，最终影响老年人的生活及生命质量；两者常相互包含，例如，大多数衰弱的老年患者符合肌少症诊断标准，而一些肌少症患者也可表现为衰弱5。所以深入掌握老年人肌少症和衰弱的发病机制、诊断筛查手段和治疗策略，可以早期干预和诊断，减少不良情况的发生率，改善生活质量。2流行病学因测定方法及纳入标准不同，肌少症和衰弱的患病率也存在差异。一研究团队分别针对衰弱和肌少症完成了两项系统评价，包括28篇衰弱相关文献，共计95 036名参与者，发现衰弱患病率为13%(95%CI：0.11，0.17)6；而针对肌少症，纳入了9篇文献，共计7 656名被调查者，显示肌少症患病率为14%(95%CI：0.09，0.20)6。国外一项纳入了100例70岁以上住院患者(女性 48 例，男性 52 例)的研究显示，肌少症占42%，衰弱占33%，19%的患者同时出现肌少症和衰弱7。尽管肌少症与衰弱的诊断标准不同，但两者既可独立存在，也可共存。3筛查方法衰弱常用的筛查工具包括：Fried 衰弱表型(frailtyphenotype，FP)8、以“累计健康缺陷”学说为依据的“衰弱指数(frailty index，FI)”9、Tilburg衰弱评估量表10等衰弱评估工具。这些量表均不同程度涵盖了老年人生理、心理、营养、生活方式、生活能力甚至社会支持等层面。其中，Fried 衰弱表型更注重描述身体衰弱，同时将肌肉萎缩视为生物基础11。Fried等12专家将衰弱定义为至少存在下列三个及以上要素：(1)体质量下降，在过去12个月内或随后出现的非故意体质量减轻 4.5 kg以上，上一年体质量减轻5%；(2)无力，基线时握力降低至最低20%，根据性别和体质量指数进行调整；(3)耐力和精力差，如自我报告的疲惫和减少的峰值摄氧量(峰值 VO2)所示；(4)步速减慢，基于4 m步态速度测试，根据性别和身高进行调整；(5)低体力活动水平，每周消耗的卡路里加权分数，根据性别调整。肌少症则是对肌肉质量、功能、强度进行测定，其中较为常见的筛查工具即 SARC-F 问卷(Strength,Assistance inwalking,Rise from a chair，Climb stairs，Falls，SARC-F)，该问卷包含 5 个维度：肌肉力量(strength)、辅助行走(assistance walking)、座椅起立(rise from a chair)、攀爬楼梯(climb stairs)和跌倒次数(fall)，按Likert3级评分法分别计02分，5个维度得分之和即为SARC-F问卷总分，总分010分，评分4分为阳性筛查试验13-14。其中的“肌肉力量测定”就是以测量握力为标准。由此看出，在筛查工具上“肌少症”和“衰弱”所含变量可能部分重叠。同样地，亚洲肌少症工作组(Asian Working Groupfor Sarcopenia，AWGS)15对肌少症的筛查方法中就包含了测量握力和步行速度(图1)16，而该项指标也是“衰弱表型”量表的构建参数。图1AWGS2019 肌少症诊断路径16Figure 1Diagnostic pathway of sarcopenia in the Asian Working Group for Sarcopenia in 2019162273海南医学2023年8月第34卷第15期Hainan Med J,Aug.2023,Vol.34,No.154发病机制4.1炎性细胞因子衰老通常与炎症水平的增加相关，尽管尚不清楚“炎症”同衰老的因果关系17。有学者表示与衰老相关的脂代谢及炎症分子(低度慢性炎症)系统功能失调可能是肌少症的关键因素18，其特点是促炎性细胞因子水平增加，抗炎性细胞因子降低。Giovannini 研究团队分析了大鼠腓肠肌中IL-15信号和 TNF-介导的凋亡途径与限制能量摄入之间的关系，结果表明衰老与大鼠腓肠肌IL-15信号转导降低有关，可能部分通过增强 TNF-介导的细胞凋亡而导致肌少症19-20。同样，促炎性细胞因子也与衰弱相关，一项白细胞介素-6与衰弱的相关性Meta 分析结果显示白细胞介素-6 水平偏高可能是衰弱的危险因素21。更有研究表明，血清 IL-6 水平与握力和步态速度呈负相关22-23。所以衰弱与肌少症可能与免疫失调相关，这也是肌少症、动脉粥样硬化、2型糖尿病、痴呆等多种增龄性疾病的病理生理学基础24。4.2低蛋白有研究显示老年住院患者前白蛋白水平266 mg/L时，前白蛋白与肌肉减少症呈负相关。也有证据显示低前白蛋白与男性肌少症有显著相关，周雨婷等25专家在老年维持性血液透析患者衰弱及其影响因素分析中表明白蛋白下降等多重因素可促进衰弱的发展。4.3内分泌因素随年龄增长，促性腺激素释放激素(GnRH)分泌发生变化，睾酮水平以每年约1%的速度下降。有证据表明睾酮能改善老年肌少症患者的功能26，较高的雄激素水平可能是老年男性免于衰弱的保护因素。同样地，雌激素也可影响骨骼肌力量，有研究表明低雌激素水平的小鼠表现出骨骼肌力量的下降，并且这种影响可以通过雌激素替代疗法(ERT)逆转27。但该说法仍有存疑，例如在一项纳入了9项研究，共涉及2 476名绝经后妇女的Meta分析中，得出了相矛盾的结论28。此外，有学者指出，非雄激素合成代谢激素如胰岛素样生长因子 1(IGF-1)、维生素D与中老年男性的衰弱状态变化独立相关。尽管有实验证据显示激素治疗联合阻力训练可以改善患者的肌肉力量，但仍慎用，例如，雌激素替代疗法可增加乳腺癌、中风、血栓栓塞、卵巢肿瘤的发生率29。4.4氧化应激肌少症本质上是由于蛋白质周转的改变导致蛋白质合成和降解之间的不平衡，当蛋白质降解多于合成时就会发生肌少症30，氧化应激在这一过程中起着重要作用。氧化蛋白的积累和蛋白质稳态改变会导致肌肉质量的丧失、运动单位的丧失、单个肌肉纤维的丧失、神经肌肉连接的结构改变和碎裂以及肌肉神经支配受损31。而肌肉质量下降所致的活动量、握力下降也可促进衰弱的发生。5临床表现肌少症与衰弱均包含以机体功能受损为特点，主要包括机体平衡障碍、步速下降以及肌力降低(图 2)32。肌少症侧重于肌肉功能减退及肌肉质量减少；衰弱综合征除表现出与肌肉相关的身体活动能力降低外，还包含心理、认知障碍、社交孤立等方面；因而有学者认为肌少症是衰弱综合征的早期表现之一。图2衰弱综合征与肌少症的临床表现33Figure 2Clinical manifestations of frailty syndrome and sarcopenia332274Hainan Med J,Aug.2023,Vol.34,No.15海南医学2023年8月第34卷第15期6干预措施6.1运动干预有Meta 分析证实，运动干预同样可以有效改善衰弱老人的步态能力和平衡能力、降低跌倒风险33。国内专家通过养老机构老年人进行奥塔戈壁运动(起源于新西兰，主要包锻炼肌力和平衡力、步行巩固锻炼效果两部分，整个过程为期1年，康复师全程跟踪及调整)，显示干预组移动能力、下肢肌力、平衡能力和衰弱状况均显著改善(P0.05)34-35。一项纳入了2 668份记录的 Meta 分析同样发现运动干预可能在改善肌肉质量/肌肉力量和步行速度方面发挥作用36。6.2营养干预6.2.1蛋白质及氨基酸杨杰等37通过调查1 693名老年人得出，衰弱老年人膳食模式的总能量、蛋白质、脂肪和膳食纤维等摄入量偏低，食用豆制品、油脂类及深海鱼等海产品严重不足。这种膳食模式同样可造成营养不良，进而引起肌少症。补充必须氨基酸(EAA)和-羟基-甲基丁酸(HMB)可改善肌肉质量和功能38。6.2.2维生素D有Meta分析表明较低的25(OH)D水平与衰弱严重程度的增加显著相关39。老年人肌少症口服补充中国专家共识(2019)40也提出维生素D营养补充剂能够使肌少症患者在改善肌肉力量和步态方面获益。另一项针对维生素D水平与衰弱表型的相关性分析中也显示维生素D缺乏与衰弱综合征密切相关41。7小结肌少症与衰弱综合征虽在发病机制、评估方法等方面存在重叠，但同衰弱相比，肌少症更加侧重于骨骼肌减少及肌肉质量下降，而衰弱构建时涉及到的变量及临床表现更加宽泛；由于衰弱的评估工具不同，所含参数也会不同，所以衰弱的治疗策略更加复杂及个体化。无论肌少症还是衰弱，都要强调早期筛查、预防为主、早期治疗，减少半失能、失能患者的患病率，向健康老龄化目标迈进。参考文献1Zhang J,Hu HX,Sun C,et al.Frailty status 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