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      Physical activity and exercise: Strategies to manage frailty

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          Abstract

          Frailty, a consequence of the interaction of the aging process and certain chronic diseases, compromises functional outcomes in the elderly and substantially increases their risk for developing disabilities and other adverse outcomes. Frailty follows from the combination of several impaired physiological mechanisms affecting multiple organs and systems. And, though frailty and sarcopenia are related, they are two different conditions. Thus, strategies to preserve or improve functional status should consider systemic function in addition to muscle conditioning. Physical activity/exercise is considered one of the main strategies to counteract frailty-related physical impairment in the elderly. Exercise reduces age-related oxidative damage and chronic inflammation, increases autophagy, and improves mitochondrial function, myokine profile, insulin-like growth factor-1 (IGF-1) signaling pathway, and insulin sensitivity. Exercise interventions target resistance (strength and power), aerobic, balance, and flexibility work. Each type improves different aspects of physical functioning, though they could be combined according to need and prescribed as a multicomponent intervention. Therefore, exercise intervention programs should be prescribed based on an individual's physical functioning and adapted to the ensuing response.

          Highlights

          • Intrinsic capacity close to disability threshold and low potential recovery due to low functional reserve lead to frailty.

          • Frailty follows from the combination of several impaired physiological mechanisms affecting multiple organs and systems.

          • Exercise reduces age-related oxidative damage and inflammation and improves mitochondrial function among other benefits.

          • Multicomponent intervention should be considered in order to impact different aspects of physical function in the elderly.

          • Exercise interventions should be prescribed based on individual’s physical functioning and adapted to the ensuing response.

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          Most cited references233

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          IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040.

          To produce current estimates of the national, regional and global impact of diabetes for 2015 and 2040.
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            Integrative biology of exercise.

            Exercise represents a major challenge to whole-body homeostasis provoking widespread perturbations in numerous cells, tissues, and organs that are caused by or are a response to the increased metabolic activity of contracting skeletal muscles. To meet this challenge, multiple integrated and often redundant responses operate to blunt the homeostatic threats generated by exercise-induced increases in muscle energy and oxygen demand. The application of molecular techniques to exercise biology has provided greater understanding of the multiplicity and complexity of cellular networks involved in exercise responses, and recent discoveries offer perspectives on the mechanisms by which muscle "communicates" with other organs and mediates the beneficial effects of exercise on health and performance.
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              Frailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: a prospective analysis of 493 737 UK Biobank participants

              Summary Background Frailty is associated with older age and multimorbidity (two or more long-term conditions); however, little is known about its prevalence or effects on mortality in younger populations. This paper aims to examine the association between frailty, multimorbidity, specific long-term conditions, and mortality in a middle-aged and older aged population. Methods Data were sourced from the UK Biobank. Frailty phenotype was based on five criteria (weight loss, exhaustion, grip strength, low physical activity, slow walking pace). Participants were deemed frail if they met at least three criteria, pre-frail if they fulfilled one or two criteria, and not frail if no criteria were met. Sociodemographic characteristics and long-term conditions were examined. The outcome was all-cause mortality, which was measured at a median of 7 years follow-up. Multinomial logistic regression compared sociodemographic characteristics and long-term conditions of frail or pre-frail participants with non-frail participants. Cox proportional hazards models examined associations between frailty or pre-frailty and mortality. Results were stratified by age group (37–45, 45–55, 55–65, 65–73 years) and sex, and were adjusted for multimorbidity count, socioeconomic status, body-mass index, smoking status, and alcohol use. Findings 493 737 participants aged 37–73 years were included in the study, of whom 16 538 (3%) were considered frail, 185 360 (38%) pre-frail, and 291 839 (59%) not frail. Frailty was significantly associated with multimorbidity (prevalence 18% [4435/25 338] in those with four or more long-term conditions; odds ratio [OR] 27·1, 95% CI 25·3–29·1) socioeconomic deprivation, smoking, obesity, and infrequent alcohol consumption. The top five long-term conditions associated with frailty were multiple sclerosis (OR 15·3; 99·75% CI 12·8–18·2); chronic fatigue syndrome (12·9; 11·1–15·0); chronic obstructive pulmonary disease (5·6; 5·2–6·1); connective tissue disease (5·4; 5·0–5·8); and diabetes (5·0; 4·7–5·2). Pre-frailty and frailty were significantly associated with mortality for all age strata in men and women (except in women aged 37–45 years) after adjustment for confounders. Interpretation Efforts to identify, manage, and prevent frailty should include middle-aged individuals with multimorbidity, in whom frailty is significantly associated with mortality, even after adjustment for number of long-term conditions, sociodemographics, and lifestyle. Research, clinical guidelines, and health-care services must shift focus from single conditions to the requirements of increasingly complex patient populations. Funding CSO Catalyst Grant and National Health Service Research for Scotland Career Research Fellowship.
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                Author and article information

                Contributors
                Journal
                Redox Biol
                Redox Biol
                Redox Biology
                Elsevier
                2213-2317
                20 March 2020
                August 2020
                20 March 2020
                : 35
                : 101513
                Affiliations
                [a ]Servicio de Histología-Investigación, Unidad de Investigación Traslacional en Cardiología (IRYCIS-UFV), Hospital Universitario Ramón y Cajal, Madrid, Spain
                [b ]Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain
                [c ]Fundación para la Investigación Biomédica del Hospital Universitario de Getafe, Getafe, Spain
                [d ]Servicio de Geriatría, Hospital Universitario de Getafe, Getafe, Spain
                Author notes
                []Corresponding author. Servicio de Geriatría, Hospital Universitario de Getafe, Ctra de Toledo km 12,500, 28905, Getafe, Spain. leocadio.rodriguez@ 123456salud.madrid.org
                Article
                S2213-2317(20)30117-8 101513
                10.1016/j.redox.2020.101513
                7284931
                32234291
                91660e3e-7201-4fd4-b8a9-c6805609cd01
                © 2020 Published by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 24 January 2020
                : 13 March 2020
                : 17 March 2020
                Categories
                Article

                aging,frailty,physical activity,exercise,oxidative stress,multicomponent intervention

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