The purpose of this project is to identify biomarkers that are individually,and in combination, associated with diverse forms of life challenges and psychologicaland social factors characterizing persons from young adulthood into old age. Cumulative adversity with limited compensating advantages is hypothesized to be reflected in multiplebiological indicators of dysregulation. Conversely, the maintenance of high levels of wellbeing in the face of life's challenges is hypothesizedto be reflected in biological indicators of high levelsof functioning across multiple systems. Biomarker data collection will be carried out at 3 General Clinical Research Centers (at UCLA, University of Wisconsin, and Georgetown University) on a sub-sample of the MIDUS population (N=1350) and on a sub-sample of the Milwaukee African-American sample (N=200). The biomarkers reflect functioning of the hypothalamic-pituitary-adrenalaxis, the autonomic nervous system, the immunesystem, cardiovascular system, and metabolic processes. In addition to average/resting levels of such biomarkers, a laboratory cognitive and orthostatic challenge study is accompanied by assessments of salivary cortisol over time, heart-rate variability, and blood pressure dynamics. The quality of interpersonal relationships, the structuring of work experience and associated opportunities (or the lack thereof) for career advancement, a personal sense of purpose and personal growth, and the possession (or lack thereof) of effective strategies for management of diverse and often unanticipated life challenges are all phenomenathat have been associated with biological responses, usually focused on one, or at most two, measures at a time. We will assess associations between responses on multiple biomarkers individually, and in combination, with individual challenges and complex profiles reflecting cumulative challenges and a diversity of psychosocial factors and health characteristics. The integration of evidence about psychosocial and biological interrelationshipsfacilitates understanding of the factors associated with resilience and the maintenance of high levels of functioning. This, in turn, can provide a more rigorous foundation for multi-faceted health promotion programs in the future and facilitate understanding of the pronounceddeclines in disability amongthe elderly that have been occurring over the past two decades.