Fifteen years of progress in understanding frailty and health in aging.

The notion of frailty has evolved for more than 15 years. Although there is no consensus definition, frailty reflects a state of increased vulnerability to adverse health outcomes for individuals of the same chronological age. Two commonly used clinical tools, the frailty index and the frailty phenotype, both measure health-related deficits. The frailty index is a ratio of the number of deficits that an individual has accumulated divided by all deficits measured, whereas the phenotype specifies frailty as represented by poor performance in three of five criteria (i.e., weight loss, exhaustion, weakness, slowness, lack of activity). From human studies, animal models of both approaches have been developed and are beginning to shed light on mechanisms underlying frailty, the influence of frailty on disease expression, and new interventions to attenuate frailty. Currently, back-translation to humans is occurring. As we start to understand subcellular mechanisms involved in damage and repair as well as their response to treatment, we will begin to understand the molecular basis of aging and, thus, of frailty.