Stress is a natural and universal part of life. However, studies that use model systems to investigate the biological mechanisms underlying the aging process (i.e., the hallmarks of aging) and interventions to retard it do not usually integrate exposures to stressors, which limits the translatability of their findings. The overarching objective of this notice of funding opportunity (NOFO) is to invite applications proposing research that incorporates exposures to a stressor(s) during the post-development period (adulthood) into studies of aging processes. Research proposed in the initial, exploratory (R61) phase will seek to determine whether exposure to a stressor(s) (e.g., physical, social, and/or environmental stressors of well-defined duration, intensity, and timing) during adulthood result in measurable changes in one or more of the hallmarks of aging. The second, developmental (R33) phase will then expand upon findings yielded in the R61 phase to determine the impacts of the stressor(s) on lifespan, healthspan, resilience, and/or interactions with other input variables such as genotype, diet, interventions, etc. Applicants can propose to employ in vitro systems; laboratory animals; or well-characterized wild, captive, free-ranging, or domesticated animal populations. Funded projects will receive up to two years of R61 support and may also receive up to three years of R33 support (contingent upon NIAs determination of the success in achieving R61 milestones, NIA priorities, and availability of funds).