ABSTRACT – BIOMARKER PROJECT The Biomarker Project plays a central role in the MIDUS efforts to understand aging as an integrated biopsychosocial process. Our prior biomarker data have received widespread engagement from the scientific community: 403 publications have been generated, 162 of which appeared since 2019. The goal going forward is to build on this momentum by collecting a 2nd wave of longitudinal data on the Refresher subsample (n=647), and a 4th wave of longitudinal data on the Core subsamples (n=630), for a total projected N=1,277. We will repeat our comprehensive battery of biomarkers (neuroendocrine, inflammatory, glucose metabolism, cardiovascular, musculoskeletal) plus add new measures related to Alzheimer’s Disease and Related Dementias (ADRD), including amyloid beta (Aβ40, Aβ42), neurofilament light (NFL), and P-tau, along with a new measure of chronic inflammation (suPAR). We will also add the Montreal Cognitive Assessment (MoCA) and a hearing test. We will investigate hypotheses about the effects of socioeconomic and psychosocial disadvantage on subsequent change in biology, predicting that those exposed to greater cumulative adversity will show heightened biological risk over time and greater functional impairment. We will also investigate the role of psychosocial resources in moderating (mitigating) against the adverse health consequences of socioeconomic and racial disparities. We will exploit the MIDUS design involving two national samples (Core, Refresher) unfolding in time to examine widening socioeconomic status differential in health outcomes in same-aged groups across different historical periods. Included in these analyses will be stress exposures related to the Great Recession (previously assessed) and newly assessed hardships of the COVID-19 pandemic. Viewed comparatively, three key features distinguish the MIDUS Biomarker Project from other U.S. studies. First, it will provide 3 waves of biological data over 20 years in the Core national sample and 2 waves of biological data over 10 years in the Refresher national sample, all obtained on mid-life adults at baseline. Second, the biomarkers collected in MIDUS are far richer than any other U.S. population-based sample. Third, the extensive survey data of MIDUS – encompassing decades of prospective information on socioeconomic, psychosocial, and behavioral aspects of participants’ lives -- provide unique opportunities for testing how these factors combine to account for who has maintained healthy biological regulation and functional health across time, while others have shifted toward clinically significant biological risk, or moved from pre-disease to disease states. The MIDUS biomarker measures are also prominently featured in other projects (Survey, Daily, Genomics) of this U19 application as well as the components (Cognitive, Affective Neuroscience, ADRD Neuroscience) of the Ancillary U01 application.