QUANTIFICATION OF BIOLOGICAL AGING FOR TESTING GEROPROTECTIVE INTERVENTIONS: EXPOSURES THAT SHORTEN HEALTHSPAN

Therapies that target hallmarks/pillars of aging, called geroprotectors, extend healthspan(definition) in laboratory animals. A challenge to translating geroprotective therapies to extend human healthspan is that clinical trials must focus on older persons, in whom intervention may come too late, or plan for decades of follow-up. Surrogate endpoints for healthspan would allow geroprotectors to be trialed in midlife humans in years rather than decades. Methods to quantify biological aging, the decline in system integrity thought to mediate age-related morbidity and mortality, could provide such surrogate endpoints. We analyzed physiology- and genomics-based measures of biological aging in young, midlife, and older adults in the US, UK, and NZ. Findings show modest differences between measures of biological aging in prediction of functional and mortality outcomes, but marked differences in sensitivity to social and health-behavior exposures known to shorten healthspan. Findings highlight need for attention to social determinants of health in geroscience research.