Cellular Senescence and the Biology of Aging, Disease, and Frailty

Abstract

Population aging simultaneously highlights the remarkable advances in science, medicine, and public policy, and the formidable challenges facing society. Indeed, aging is the primary risk factor for many of the most common chronic diseases and frailty, which result in profound social and economic costs. Population aging also reveals an opportunity, i.e. interventions to disrupt the fundamental biology of aging could significantly delay the onset of age-related conditions as a group, and, as a result, extend the healthy life span, or health span. There is now considerable evidence that cellular senescence is an underlying mechanism of aging and age-related conditions. Cellular senescence is a process in which cells lose the ability to divide and damage neighboring cells by the factors they secrete, collectively referred to as the senescence-associated secretory phenotype (SASP). Herein, we discuss the concept of cellular senescence, review the evidence that implicates cellular senescence and SASP in age-related deterioration, hyperproliferation, and inflammation, and propose that this underlying mechanism of aging may play a fundamental role in the biology of frailty.

Figure 1. Aging and Healthspan

Aging is the primary risk factor of the majority of chronic diseases and frailty. As a result, the period of life in good health and relatively free from the burden of disease, disability, and frailty, termed healthspan, progressively declines (A). Interventions that target the underlying biology of aging, as opposed to individual diseases, have the potential to delay the onset of age-related conditions as a group. This would have a profound impact on extending healthspan and dramatically compress the period of morbidity at the end of life (B).