CORE D: METABOLITE PHENOTYPES OF AGING ? PROJECT SUMMARY/ABSTRACT Molecular genetic approaches have led to tremendous advances in the study of the basic biology of aging, shedding light on the causes and consequences of senescence. But there remains a significant gap between our ability to identify genetic and experimental perturbations that extend lifespan, and our understanding of the mechanisms by which these perturbations extend lifespan. Metabolomics offers a relatively simple yet powerful approach to close this gap. The metabolome consists of the thousands of unique small molecules that make up the building blocks of all organisms, and its analysis has the potential to greatly enhance our ability to identify and understand the functional pathways that underlie senescence. The primary goal of Core D is to assist collaborating geroscientists in experimental design, sample collection and data analysis of accurate metabolite profiles in studies on the basic biology of aging. The statistical support provided by the core has proven to be an invaluable step in helping collaborators not only to obtain metabolomic data, but also to analyze the complex, high-dimensional datasets that arise from metabolomic profiling. This Core will work closely with Core C (Protein Phenotypes of Aging), which will be housed in the same facility, and with Core E (Invertebrate Longevity and Healthspan). Cores C and D will collaborate with Core F (Artificial Intelligence and Bioinformatics) on a novel project to develop metabolome-proteome networks for researchers interested in studying both domains simultaneously. The resources offered here include methods that can be applied to a wide range of non-model species, including humans. Core D will also play a key role in collaborative efforts between the University of Washington NSC and other NSCs throughout the country. Core D has already collaborated with three Nathan Shock centers (Albert Einstein, Oklahoma, and Alabama), and over 40 collaborating researchers around the country. This Core will devote considerable effort to hardware and software development, ensuring that we are constantly pushing the scientific boundaries in this field. The Core will also serve as a central repository for aging- related metabolomic data. In the long term, Core D will help to make age-specific metabolite phenotypes an essential and invaluable component of any study of aging phenotypes. The Core will have a major impact on biogerontology at the broadest level, making these resources available to the broadest possible community of geroscientists, and enabling our collaborators to identify new mechanistic pathways linking genes with aging, including pathways that have the potential to reveal new drug targets.
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