Adult health and longevity in the United States lag well behind other wealthy countries. Despite widening recognition of this crisis, we have only a limited understanding of its causes and few strategies to reverse them. This proposal, a renewal of the highly successful Network on Life Course Health Dynamics and Disparities in 21st Century America (NLCHDD) funded for the past five years by the National Institute on Aging, lays out a plan to further develop the scientific groundwork, human capital, and data and analytic infrastructure to answer critical questions about the U.S. health crisis. Our overarching objective over the next five years is to strengthen and focus the NLCHDD to generate new evidence and disseminate data and analytic resources to better understand the trends and disparities in U.S. adult health and longevity across the life course and in geographic context. We will do so through four specific aims. First, we will direct attention and resources toward four targeted scientific questions that will shed light on the multi-layered determinants of the troubling trends and growing disparities in U.S. adult health and longevity. These questions (described in detail in the proposal) focus on how state and local contexts?separately and collectively?shape trends and disparities in adult health and longevity across the life course. Second, we will strategically grow the interdisciplinary Network of emerging, established, and underrepresented scientists who will collaborate to investigate the key scientific questions. Third, we will provide development and training opportunities for Network scientists via pilot grants, grant proposal mentoring, working groups, and annual meetings. Fourth, we will develop and disseminate data and analytic resources to foster innovative research on the key scientific questions and advance science in this critical area. Our Network is innovative in its focus on the multilayered contextual determinants of trends and disparities in adult health and longevity across the life course; in its openness and evolving nature; in its efforts to incorporate emerging investigators with more established ones; and in its central concern for support, mentoring, and development of emerging and underrepresented scholars. This emphasis on human capital development is reflected in all aspects of the Network’s organization and operation. Our Network is also unique in its attention to focusing on research that can inform policies and interventions and provide the foundation for future research advances. Finally, our Network is unique in that it will facilitate the expansion, integration, and public dissemination of new and existing databases on population health determinants at state and local contexts. The proposed renewal Network brings together a PI team and four sites that span the U.S. with substantial experience in developing large-scale population health research and complementary scientific strengths connected to the Network?s aims. Using its complementary strengths, developmental maturity, and geographic diversity, the NLCHDD leadership and overall Network is poised to make important scientific inroads over the next five years on the U.S. population health and longevity crisis.