Elsevier

Experimental Gerontology

Volume 54, June 2014, Pages 6-13
Experimental Gerontology

Review
The Frailty Syndrome: Clinical measurements and basic underpinnings in humans and animals

https://doi.org/10.1016/j.exger.2014.01.024Get rights and content

Highlights

  • There is a lack of fundamental understanding and of animal models to study frailty.

  • We discuss key theories of frailty—cytokine dysfunction and mitochondrial disorder.

  • There is a need for objective human measures using biosensors and imaging.

  • We review recent breakthroughs correlating animal and human frailty measures.

Abstract

Frailty is an increasingly recognized syndrome resulting in age-related decline in function and reserve across multiple physiologic systems. It presents as a hyperinflammable state, characterized by high vulnerability for adverse health outcomes, such as disability, falls, hospitalization, institutionalization, and mortality. The prevalence of Frailty Syndrome (FS) is of potentially enormous significance, as it potentially affects 20–30% of adults older than 75. Cellular and molecular basis of frailty has not been elucidated.

The objective of this review is to discuss recent advances in: (i) the potential cellular and molecular basis of Frailty Syndrome, including development of new models to study it; (ii) the human and animal measures of Frailty Syndrome; and (iii) the development of objective cross-species correlates to aid the basic understanding, diagnosis, treatment and rehabilitation of Frailty Syndrome in older adults.

Section snippets

Introduction—overview of the clinical implications of the Frailty Syndrome (FS)

We live in an aging society, and the most rapidly growing segment of our population are people over the age of ninety (Anon, 2011). This relatively recent explosion of large numbers of very old people living in our communities has brought to light a new and critically important health problem—the Frailty Syndrome (FS in the text). Frailty manifests as a limited capacity to maintain homeostasis and is characterized by a clinical state of age-related biological vulnerability to stressors and

Basic cellular and molecular biology of frailty/FS, or the “unknown unknowns”

There is very little solid evidence to explain how FS occurs at the level of molecules, cells and tissues and to decisively establish that it is a molecularly distinct syndrome. The expanding number of reported biomarkers associated with FS include, but are not limited to, soluble mediators of the inflammatory response including elevated cytokines and chemokines reduced IGF-I, DHEAS and leptin, hormones, fibrin turnover and fibrinolysis, free radicals, antioxidants, macro- and micro-nutrients (

Approaches to measuring frailty

There are many approaches to the measurement of frailty developed that do not include direct measures of complex processes of dysregulation. A consensus report on frailty research design by a group of Italian and American geriatricians advocated inclusion of impairments in physiological domains that include mobility, balance, muscle strength, motor processing, cognition, nutrition, and physical activity (Ferrucci et al., 2004b). A recent systematic review also suggests that frailty could be

Conclusions and recommendations: towards the “known knowns”

FS is affecting nearly a third of older adults over 90, and is of an increasing socioeconomic importance. It is very clear from the above discussion that we have preciously few animal or tissue culture models to distinguish between the current mechanistic hypotheses of frailty and that we are not particularly good at measuring it precisely and objectively in humans. To further our basic understanding of frailty/FS and to improve diagnostics and management of this condition, we propose the

Conflict of interest

The authors have no conflicts of interests.

Funding source

This review has been generously funded by the Arizona Center on Aging and in part from the NIH ADB Contract HHSN 272201100017C (NIH/NIAID N01-AI 00017) and the Bowman Endowed Professorship in Medical Research (both to J.N-Z).

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    These authors contributed equally to this review.

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