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      A Clinical Frailty Index in Aging Mice: Comparisons With Frailty Index Data in Humans

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          Abstract

          We previously quantified frailty in aged mice with frailty index (FI) that used specialized equipment to measure health parameters. Here we developed a simplified, noninvasive method to quantify frailty through clinical assessment of C57BL/6J mice (5–28 months) and compared the relationship between FI scores and age in mice and humans. FIs calculated with the original performance-based eight-item FI increased from 0.06±0.01 at 5 months to 0.36±0.06 at 19 months and 0.38±0.04 at 28 months ( n = 14). By contrast, the increase was graded with a 31-item clinical FI (0.02±0.005 at 5 months; 0.12±0.008 at 19 months; 0.33±0.02 at 28 months; n = 14). FI scores calculated from 70 self-report items from the first wave of the Survey of Health, Ageing and Retirement in Europe were plotted as function of age ( n = 30,025 people). The exponential relationship between FI scores and age (normalized to 90% mortality) was similar in mice and humans for the clinical FI but not the eight-item FI. This noninvasive FI based on clinical measures can be used in longitudinal studies to quantify frailty in mice. Unlike the performance-based eight-item mouse FI, the clinical FI exhibits key features of the FI established for use in humans.

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          Frailty defined by deficit accumulation and geriatric medicine defined by frailty.

          As nonreplicative cells age, they commonly accumulate subcellular deficits that can compromise function. As people age, they too experience problems that can accumulate. As deficits (symptoms, signs, illnesses, disabilities) accumulate, people become more susceptible to adverse health outcomes, including worse health and even death. This state of increased risk of adverse health outcomes is indistinguishable from the idea of frailty, so deficit accumulation represents another way to define frailty. Counting deficits not only allows grades of frailty to be discerned but also provides insights into the complex problems of older adults. This process is potentially useful to geriatricians who need to be experts in managing complexity. A key to managing complexity is through instruments such as a comprehensive geriatric assessment, which can serve as the basis for routine clinical estimation of an individual's degree of frailty. Understanding people and their needs as deficits accumulate is an exciting challenge for clinical research on frailty and its management by geriatricians. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Frailty in relation to the accumulation of deficits.

            This review article summarizes how frailty can be considered in relation to deficit accumulation. Recalling that frailty is an age-associated, nonspecific vulnerability, we consider symptoms, signs, diseases, and disabilities as deficits, which are combined in a frailty index. An individual's frailty index score reflects the proportion of potential deficits present in that person, and indicates the likelihood that frailty is present. Although based on a simple count, the frailty index shows several interesting properties, including a characteristic rate of accumulation, a submaximal limit, and characteristic changes with age in its distribution. The frailty index, as a state variable, is able to quantitatively summarize vulnerability. Future studies include the application of network analyses and stochastic analytical techniques to the evaluation of the frailty index and the description of other state variables in relation to frailty.
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              Aging, frailty and age-related diseases.

              The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people.
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                Author and article information

                Journal
                J Gerontol A Biol Sci Med Sci
                J. Gerontol. A Biol. Sci. Med. Sci
                gerona
                gerona
                The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
                Oxford University Press (US )
                1079-5006
                1758-535X
                June 2014
                19 September 2013
                19 September 2013
                : 69
                : 6
                : 621-632
                Affiliations
                1Department of Pharmacology ,
                2Carleton Animal Care Facility ,
                3Department of Medicine (Geriatric Medicine) and
                4Department of Physiology and Biophysics , Dalhousie University , Halifax, Nova Scotia, Canada.
                Author notes
                Address correspondence to Susan E. Howlett, PhD, Department of Pharmacology, 5850 College Street, PO Box 15000, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2. Email: Susan.Howlett@ 123456dal.ca

                Decision Editor: Rafael de Cabo, PhD

                Article
                10.1093/gerona/glt136
                4022099
                24051346
                27b1efc5-7f2a-4516-8d63-a0b5481d7325
                © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 22 May 2013
                : 15 July 2013
                Page count
                Pages: 12
                Categories
                Original Article
                Editor's choice

                Geriatric medicine
                frailty index,deficit index,deficit accumulation,senescence.
                Geriatric medicine
                frailty index, deficit index, deficit accumulation, senescence.

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