CORE C- Abstract The Human Target Verification and Thymic Function Core (Core C) was integrated into this program to provide proof-of-concept verification, in human thymus, lymph node (LN), and T cell aging, of the targets and pathways identified by the innovative approaches and mouse models of the research projects. Assets that Core C brings to the program include the expertise of Core leaders who are widely acknowledged as world experts in human thymus biology and aging and the Duke Human Vaccine Institute (DHVI) Human Thymus Biobank that contains tissues and isolated cells from 890+ healthy human donors aged 1 day to 78 years, with ongoing collection of new specimens. Core C also provides comprehensive histology, expert board-certified pathology support, mouse and human sjTREC analysis and thymus gene expression profiling. Over the next five years of the Program, Core C will continue to accelerate proof-of-concept verification of project-identified mouse therapeutic targets/pathways in human thymus, LN, and T cell aging and independently monitor thymic output, through two focused Service Tasks or Core Aims: 1) To define, characterize, and supply human tissue panels from donors of defined age and sex to meet project-specific translation verification needs; and 2) To provide central histologic and flow cytometric analyses on human thymus and obtain data from molecular analyses on human and mouse thymus tissues. Use of Core C services in the renewal period is anticipated by all three projects. Delivery of Core C services to Projects 1-3 is a key component of overall program synergy, and very importantly, will provide critical proof-of-concept verification of applicability of mouse targets/pathways to aging in human thymus. This will facilitate project goals for rejuvenation strategies to ameliorate age- associated immune deficiencies and improve immune defense against infection and cancer as individuals age.