Core D Metabolic Phenotypes of Aging

CORE D: METABOLIC PHENOTYPES OF AGING – SUMMARY 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. Detailed metabolic information, obtained through the integration of metabolomics and mitochondrial metabolism interrogations, offers a powerful approach to close this gap. The metabolome measures the concentration of hundreds to many thousands of small molecules that make up the structural and functional building blocks of all living organisms and play an important role in not only metabolism, but also intra and inter-cellular signaling, epigenetic regulation, and protein function. Aim 1 of Core D provides a broad range of metabolite profiling methods by closely liaising with the Northwest Metabolomics Research Center. The available advanced mass spectrometry and NMR platforms provide a broad-based approach for targeted, global assays of aqueous and lipid metabolites and metabolic flux analyses for aging-related biomarker discovery and for basic systems biology research. Aim 2 provides analytical workflows for rigorous statistical analyses of aging related pathways, metabolomic clock and biomarker discovery. Core users will receive detailed training by experts on the use of multivariate statistical methods as well as metabolic pathway analysis tools to allow them to quickly access the superb capabilities in metabolomics. Aim 3 offers customizable assays of mitochondrial oxidative phosphorylation, including respiration, membrane potential, and oxidant production. These services are focused on complementing the metabolomic assays of Core D and the other Resource Cores of the UW NSC to provide a simple integrated resource to incorporate quantitative measures of mitochondrial function with multi-omics and invertebrate model technologies provided by the UW NSC. The resources provided by Core D to quantify changes in metabolic and signaling roles of metabolites in aging support the emphasis of the UW NSC on cross core collaboration for highly integrated multi-omics analyses to support impactful research into the biology of aging.