MULTISYSTEM PHYSIOLOGICAL PERSPECTIVE OF HUMAN FRAILTY AND ITS MODULATION BY PHYSICAL ACTIVITY

被引:86
作者
Taylor, Joseph A. [1 ]
Greenhaff, Paul L. [1 ,2 ]
Bartlett, David B. [3 ,4 ]
Jackson, Thomas A. [5 ]
Duggal, Niharika A. [5 ]
Lord, Janet M. [5 ,6 ,7 ]
机构
[1] Univ Nottingham, MRC Versus Arthrit Ctr Musculoskeletal Ageing Res, Queens Med Ctr, Sch Life Sci, Nottingham, England
[2] Univ Nottingham, NIHR Nottingham Biomed Res Ctr, Queens Med Ctr, Nottingham, England
[3] Duke Univ, Dept Med, Div Med Oncol, Durham, NC USA
[4] Univ Surrey, Fac Hlth & Med Sci, Dept Nutr Sci, Guildford, England
[5] Univ Birmingham, Inst Inflammat & Ageing, MRC Versus Arthrit Ctr Musculoskeletal Ageing Res, Birmingham, England
[6] Univ Hosp Birmingham, NIHR Birmingham Biomed Res Ctr, Birmingham, England
[7] Univ Birmingham, Birmingham, England
关键词
brain; cardiovascular system; exercise; frailty; inflammation; NECROSIS-FACTOR-ALPHA; BODY-MASS INDEX; QUALITY-OF-LIFE; MULTIFACTORIAL INTERDISCIPLINARY INTERVENTION; CARDIOVASCULAR-DISEASE ENTERPRISES; ADIPOSE-TISSUE COMPARTMENTS; MILD COGNITIVE IMPAIRMENT; SKELETAL-MUSCLE STRENGTH; DWELLING OLDER-ADULTS; SMALL VESSEL DISEASE;
D O I
10.1152/physrev.00037.2021
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
"Frailty" is a term used to refer to a state characterized by enhanced vulnerability to, and impaired recovery from, stressors compared with a nonfrail state, which is increasingly viewed as a loss of resilience. With increas-ing life expectancy and the associated rise in years spent with physical frailty, there is a need to understand the clinical and physiological features of frailty and the factors driving it. We describe the clinical definitions of age -related frailty and their limitations in allowing us to understand the pathogenesis of this prevalent condition. Given that age-related frailty manifests in the form of functional declines such as poor balance, falls, and immo-bility, as an alternative we view frailty from a physiological viewpoint and describe what is known of the organ -based components of frailty, including adiposity, the brain, and neuromuscular, skeletal muscle, immune, and cardiovascular systems, as individual systems and as components in multisystem dysregulation. By doing so we aim to highlight current understanding of the physiological phenotype of frailty and reveal key knowledge gaps and potential mechanistic drivers of the trajectory to frailty. We also review the studies in humans that have intervened with exercise to reduce frailty. We conclude that more longitudinal and interventional clinical studies are required in older adults. Such observational studies should interrogate the progression from a nonfrail to a frail state, assessing individual elements of frailty to produce a deep physiological phenotype of the syndrome. The findings will identify mechanistic drivers of frailty and allow targeted interventions to diminish frailty progression.
引用
收藏
页码:1137 / 1191
页数:56
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