Age-related frailty is a late stage manifestation of degenerative aging, a state of physical weakness and vulnerability that precedes death. Aging is the accumulation of damage and dysfunction, and the burden of such damage and dysfunction needed to produce frailty is one step removed from the amount needed to cause one of the many forms of fatal system failure that cause human mortality. Whether death is eventually due to cardiovascular disease, dementia, or kidney failure, frailty is a proximate indicator.
In this long-term population-based prospective cohort comprising 9,912 participants, we evaluated the risk of mortality according to longitudinal repeated measurements of Frailty Index (FI). Both levels of FI and the proportions of frail participants gradually increased with age and there was significant variability in the progression of frailty. We observed clear dose-response relationships between FI values and all-cause, cancer, and cardiovascular disease (CVD) mortality, with associations being substantially stronger and consistent across various lengths of follow-up when FI was considered as a time-varying predictor variable rather than being based on a single measurement at baseline.
The increase in prevalence of frailty with age is well established in both cross-sectional and longitudinal studies in aging research. For example, in a cross-sectional study among 993 adults aged 70+ conducted in Spain, prevalence of frailty (measured by Fried frailty) was reported to be 7.1%, 14.5%, 29.7%, 31.8%, and 43.2%, in participants aged 70-74, 75-79, 80-84, 85-89 and over 90 years, respectively. In a cohort study conducted in 350 older adults (≥65 years) residing in long-term care facilities in Korea, the prevalence of frailty (measured by Fried frailty) increased from 25.8% to 35.2% during three years of follow-up.The increase in frailty prevalence with age is in line with the expected consequence of the cumulative decline in multiple physiological systems occurring at older age.
Nevertheless, in agreement with results from other recent studies, our study demonstrates that there is substantial inter-individual variability in development and progression of frailty with increasing age, including the possibility of regression of frailty. A variety of factors contributes to the development of frailty and frailty transitions, including nutritional status, environmental factors, diseases, and psychological factors. Therefore, these changeable characteristics make frailty a comprehensive and reversible health condition.