Frailty as a Model of Aging

Frailty has been seen by clinicians and investigators as a late-life syndrome of weight loss and declines in strength and vigor. In addition, it has been characterized as a syndrome of extreme vulnerability to external stressors, and one that marks high risk for poor clinical outcomes. Over the past few years, several groups of investigators have attempted to more rigorously define frailty, and to identify physiologic and molecular contributing factors. Many of these definitions involve clinical findings of weight loss, strength decline, and low levels of activity, and are, as such, characterized as physical or musculoskeletal frailty. Other investigators have tried to better identify the cognitive components of frailty. This chapter will describe several recent models of frailty and the validation of these models. In addition, hypotheses related to the biologic underpinnings of frailty, and how these biologic characteristics may be related to the biology of aging, will be presented. Finally, a discussion of the utility of these models in clinical research and the potential relevance for further biologic discovery will be discussed.