The degree of frailty as a translational measure of health in aging

Frailty is a multiply determined, age-related state of increased risk for adverse health outcomes. We review how the degree of frailty conditions the development of late-life diseases and modifies their expression. The risks for frailty range from subcellular damage to social determinants. These risks are often synergistic—circumstances that favor damage also make repair less likely. We explore how age-related damage and decline in repair result in cellular and molecular deficits that scale up to tissue, organ and system levels, where they are jointly expressed as frailty. The degree of frailty can help to explain the distinction between carrying damage and expressing its usual clinical manifestations. Studying people—and animals—who live with frailty, including them in clinical trials and measuring the impact of the degree of frailty are ways to better understand the diseases of old age and to establish best practices for the care of older adults.