The VLS is a long-term, large-scale, and multi-faceted longitudinal investigation of human aging. Incorporating biomedical approaches, leading-edge technologies, and epidemiological perspectives, the VLS evaluates and tracks actual cognitive, health, functional and lifestyle trajectories leading to outcomes that can be classified as normal, resilient, exceptional, impaired, or dementia. Our studies examine these differential brain and cognitive changes as a function of interactions among multiple “biomarkers” of both risk and protection. Among these dynamically interacting biomarkers are those representing selected aspects of biological, health, genetic, metabolic, vascular, lifestyle, physical fitness, cognitive activity, sex/gender, and demographic domains