New horizons in frailty: Ageing and the deficit-scaling problem

Division of Geriatric Medicine, Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Age and Ageing (Impact Factor: 3.64). 06/2013; 42(4). DOI: 10.1093/ageing/aft059
Source: PubMed


All the current frailty measures count deficits. They differ chiefly in which items, and how many, they consider. These differences are related: if a measure considers only a few items, to define broad risks those items need to integrate across several systems (e.g. mobility or function). If many items are included, the cumulative effect of small deficits can be considered. Even so, it is not clear just how small deficits can be. To better understand how the scale of deficit accumulation might impact frailty measurement, we consider how age-related, subcellular deficits might become macroscopically visible and so give rise to frailty. Cellular deficits occur when subcellular damage has neither been repaired nor cleared. With greater cellular deficit accumulation, detection becomes more likely. Deficit detection can be done by either subclinical (e.g. laboratory, imaging, electrodiagnostic) or clinical methods. Not all clinically evident deficits need cross a disease threshold. The extent to which cellular deficit accumulation compromises organ function can reflect not just what is happening in that organ system, but deficit accumulation in other organ systems too. In general, frailty arises in relation to the number of organ systems in which deficits accumulate. This understanding of how subcellular deficits might scale has implications for understanding frailty as a vulnerability state. Considering the cumulative effects of many small deficits appears to allow important aspects of the behaviour of systems close to failure to be observed. It also suggests the potential to detect frailty with less reliance on clinical observation than current methods employ.

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    • "The ultimate goal of ageing research should be to increase health-span, mitigating a lifespan burdened by morbidity. To this end, frailty is a useful indicator of overall health deficit, describing a physiological loss of reserve capacity and reduced resistance to stressors [1, 2]. It predicts adverse health states such as hospitalisation, dependency and mortality better than chronological age [3], and is increasingly important given the ageing global population with UN estimates of 1.2 billion people aged over 60 years by 2025 [4]. "
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    • "The dominant view of cellular aging is that subcellular, cellular, and intercellular damage progress to deficits at the level of tissue and organs (which might be identified by laboratory or imaging tests before they become clinically apparent), and eventually at higher level functions, including functional dependence, falls, immobility, and cognitive impair- ment[21 && ]. The mechanisms of this scaling process are complex and not yet fully understood, but the notion that health problems make an individual more likely to develop further health problems is a plausible one[22]. Problems in one physiological system also contribute to vulnerability in others, and though the individual effects of a deficit can be small their cumulative effects can be large[23,24 & ]. "
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    ABSTRACT: Purpose of review: Effective therapies have transformed HIV infection into a chronic disease, and new problems are arising related to aging. This article reviews the aging process, age-related deficit accumulation and frailty, and how these might be affected by chronic HIV infection. Recent findings: Aging is characterized by acceleration in the rate of unrepaired physiologic damage an organism accumulates. HIV infection is associated with many factors that might affect the aging process, including extrinsic behavioral risk factors and co-infections, and multiple intrinsic factors, including intercellular communication, inflammation, and coagulation pathways. Whether each factor affects the aging process, they likely result in an increase in the risk of adverse health outcomes, and so give rise to frailty, likely with several clinical manifestations. Summary: Age-related deficit accumulation is influenced by both the background or environmental rate of insults an organism sustains and the efficacy of intrinsic damage control and repair mechanisms. Both processes are likely affected in people living with HIV infection.
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    • "Although many different measurement instruments have been proposed, most commentary generally has focussed on two approaches, deficit accumulation and the frailty phenotype (reviewed by de Vries et al.) (7). The deficit accumulation approach we propose here for use in mice accords with the deficit accumulation approach used in many previous studies in humans (2,4,53). It includes integrative measures such as grooming, strength, mobility, and measures of discomfort, so it measures deficits constituted broadly. "
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    Full-text · Article · Sep 2013 · The Journals of Gerontology Series A Biological Sciences and Medical Sciences
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