Genetics of frailty: A longevity perspective

Abstract

Frailty is a complex late life phenotype characterized by cumulative declines in multiple physiological systems that increases the risk for disability and mortality. The biological changes associated with aging are risk factors for frailty as well as for complex diseases; whereas longevity is assumed to be an outcome of protective biological mechanisms. Understanding the interplay between biological alterations associated with aging and protective mechanisms associated with longevity in the context of frailty may help guide development of interventions to increase healthspan and promote successful aging. The complexity of these phenotypes and relatively low heritability in studies are the main roadblocks in deciphering genetic mechanisms of these age associated conditions. We review genetic research related to frailty, and discuss the possible intertwined biology of frailty and longevity.

Fig 1.

Genes associated with longevity phenotypes in largescale genome wide association studies.

Fig 2.

Different models for interaction of longevity and frailty. (a) In usual survivor longevity associated protection conferred by Geroprotector, including longevity factors (green) is less and accumulation of insults (red) leads to decrease in healthspan as well as lead to disabilities, frailty, and comorbidities finally leading to death. (b) In long-lived healthy individual have more Geroprotectors acting throughout life preventing insults as well as increasing stretch of healthspan as well as life span. Frailty and other comorbidities are confined to small time span. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)”