ENHANCING THE CALERIE NETWORK TO ADVANCE AGING BIOLOGY ABSTRACT: In direct response to PA-20-071, Advanced-Stage Development and Utilization of Research Infrastructure for Interdisciplinary Aging Studies), we propose to enhance and grow the CALERIE Research Network into a self- sustaining infra-structure of samples, data, and aging biology investigators. The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) was a randomized controlled trial designed to assess the effects in humans of two years of sustained caloric restriction without enforced changes of dietary composition. The overall objective was to elucidate underlying biological mechanisms and mediators of primary and secondary human aging. The rigorous design and execution of the CALERIE intervention produced an invaluable resource, including comprehensive phenotypic data that are coupled to biological samples. To ensure continued use of these samples and data, we describe a plan to create a self-sustained CALERIE Network. Our aims are to advance aging research through enhanced 1) utilization, 2) development and interdisciplinary growth of the CALERIE Research Network. Utilization of CALERIE resources will be promoted and stewarded by a Steering Committee, an NIA Biobank representative, NIA-supported Networks and Centers, annual workshops and working groups. These efforts will ensure best use of remaining CALERIE samples as well as incorporation of new data into a complex multi-level database. CALERIE Network inter- disciplinary growth will be fostered by attracting new and junior aging biologists to pilot projects, career development activities, and a rich pipeline of integrative systems biology projects. By developing more investigators, projects, and disciplines, new data and samples will be generated and will perpetuate the aging biology scientific cycle. Thus, completion of these aims should yield a mature, sustainable infrastructure that maintains and oversees CALERIE samples and data, perpetuates CALERIE ancillary integrative investigations, and contributes to overall advancement of understanding of human aging biology.