PROJECT SUMMARY – Molecular Measures Core (MMC) The Molecular Measures Core (MMC) provides a centralized resource, analytical tools and expertise to measure a broad array of molecular analytes in support of Duke OAIC projects in their work to understand and optimize reserve and resilience. The MMC has served as an integral Resource Core in support of the Duke OAIC since 2006. For this funding cycle, the MMC will focus on molecular analyses that provide mechanistic insights into resiliencies at the cellular, tissue or organ levels that are expected to increase our understanding of the means to optimize reserve and resilience at the whole person level. The MMC will provide molecular analytic, mentoring and consultative support for a host of Research Education Component (REC) Scholar Projects, Pilot/Exploratory Studies (PESs) and External Projects (EPs). These projects test hypotheses related to aging across the lifespan, mechanisms underlying reserve and resilience in human, primates and in vitro, and involve a range of patient and sample types. The MMC is capable of providing services to measure a broad array of cellular, molecular, biochemical and metabolic factors. The most pertinent Core services in the next funding cycle will include molecular measures of inflammation, targeted and untargeted metabolomics, epigenetic measures of miRNAs related to longevity, molecular measures of biological age, and analyses of extracellular vesicles. In addition, the MMC will conduct a Developmental Project (MMC-DP) to develop new capabilities for profiling coronavirus serologies to evaluate prior SARS-CoV2 infection as a modifier of cardiorespiratory and metabolic reserve in a substudy of the MoTrPAC cohort (Years 1-2). This MMC-DP validated serological testing will be made available to the Duke OAIC researchers and projects in the latter years of funding. The MMC will also use the senescent model system (developed in the current funding period) to test interventions including mimics and inhibitors of ‘longevity miRNA’ and extracellular vesicles to promote resilience (Years 1-5). In addition, the MMC will provide Pathways Analysis (using Ingenuity Systems) of molecular data to identify potential biological networks involved in reserve and resilience. The exciting focus on resilience in this cycle provides an opportunity to explore the latest theories on aging that are particularly amenable and suited to evaluation by molecular approaches. The application of molecular and pathways analyses to these projects are expected to provide objective insights into the mechanisms underlying reserve and resilience in support of the mission of the Duke OAIC.