Connecting age-related biological decline to frailty and late-life vulnerability. Frailty: pathophysiology, phenotype and patient care.


 Frailty is an important construct in aging which allows for the identification of the most vulnerable subset of older adults. At least two conceptual models of frailty have been developed that have in turn facilitated the development of multiple frailty screening tools. This has enabled the study of populations of frail and nonfrail older adults, and facilitated the risk assessment for adverse health outcomes. In addition, using the syndromic approach to frailty, numerous biological hypotheses have been tested, which have identified chronic inflammatory pathway activation, hypothalamic-pituitary-adrenal axis activation, and sympathetic nervous system activity as important in the development of frailty. In addition, age-related molecular changes related to autophagy, mitochondrial decline, apoptosis, senescent cell development, and necroptosis likely contribute to the heterogeneous phenotype of frailty. The recent development of a frail mouse model with chronic inflammatory pathway activation has helped to facilitate further whole organism biological discoveries. The following article attempts to create an understanding of the connections between these age-related biological changes and frailty.
 © 2015 Nestec Ltd., Vevey/S. Karger AG, Basel



The biology of aging and frailty


In developing and validating the concept of frailty as a geriatric syndrome, it has been necessary to distinguish the clinical expression of frailty from normal age-related changes and other age-related disease pathologies. A framework for excluding potentially confounding disease and a working clinical tool to diagnose frailty have been provided. The associations between frailty and other pathophysiologies has also been shown. However, investigating the underlying biologic basis for the geriatric syndrome of frailty by studying basic homeostatic pathways and mechanisms has not proceeded at the same rate. The following article provides an overview of the homeostatic pathways emphasized in research on aging and explains how this science may help to stimulate frailty research.

Copyright © 2011 Elsevier Inc. All rights reserved.

Inflammation, coagulation, and the pathway to frailty


There are inevitable physiologic changes associated with advancing age, yet for some people these changes are exaggerated, and as a result a phenotype emerges recognized as “frailty.” Why some people become frail and others do not remains incompletely understood. Although chronic illnesses are common among frail elderly persons, some will develop all of the phenotypic features without a diagnosed underlying disease. It has been recognized that certain proinflammatory cytokines and coagulation factors are elevated to a greater extent in those who are frail than in age-matched nonfrail individuals. In this review, we provide an overview of current research in the biology of frailty with particular emphasis on the role of inflammatory pathways and disordered coagulation in its pathogenesis.

Biological markers and the molecular biology of frailty. Longevity and frailty.


Walston, Jeremy D. Biological markers and the molecular biology of frailty. Longevity and frailty. Springer, Berlin, Heidelberg, 2005. 83-90.


Biomarkers of frailty in older persons

Trajectories of health and functioning with age show extreme variability among different individuals. Normal aging implies a progressive decline of physiological reserve and ability to compensate, but it is compatible with autonomy over the entire life span. In frail, older persons the decline in functional reserve is accelerated and compensatory mechanisms start failing, with high risk of homeostasis disruption and consequent negative health outcomes. Frailty is currently conceptualized as an age-related alteration in physiology and pathology that results into a typical constellation of signs and symptoms. Although current attempts to identify frail, older individuals for clinical purposes are based on measures of mobility and motor performance, candidate biological markers that may characterize the frailty syndrome start to emerge in the literature. These potential markers include, but are not limited to, soluble mediators of the inflammatory response, hormones, free radicals, antioxidants and macro- and micro-nutrients. This is a research area undergoing a rapid, dynamic development that may profit from new ways of defining disability outcomes in epidemiological studies of the elderly.