Figure 2.

Mechanisms of frailty. The physiologic underpinnings of frailty are complex and involve a range of interacting elements. A number of physiological perturbations have been noted to be common among frail individuals, but none have specifically been shown to be necessary for the development of frailty. Frailty-related changes occur across multiple biological systems as both an innate element of aging and a response to environmental exposures. These systems interact through a network of interconnected feedback loops to produce the vulnerable state of frailty, including disability, dependence, and adverse health outcomes, particularly following stress. ADL indicates activities of daily living; ADMA, asymmetric dimethylarginine; CRP, C-reactive protein; DHEA, dehydroepiandrosterone; HRQOL, health-related quality of life; IADL, instrumental activities of daily living; IGF1, insulin-like growth factor 1; IL, interleukin; TNFα, tumor necrosis factor α.