Comparative Bioenergetics of Aging

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Project Summary The University of Alabama at Birmingham (UAB) proposes to renew a Nathan Shock Center of Excellence in the Basic Biology of Aging focused on comparative bioenergetics and aging. Energetics is comprehensively defined for this purpose as the study of the causes, mechanisms, and consequences of the acquisition, storage, and utilization of metabolizable energy. Comparative energetics is the study of metabolic processes at multiple scales and across multiple species, in this case as it relates to health and aging. Nearly a century of aging research has reinforced the link between energetics and aging. In modern terms, this link is reified as dysregulated mitochondrial function, metabolic signaling, and nutrient responsiveness. The twin objectives of the Center will be to 1) explore in greater depth and detail than previously possible the complex relationship among cellular and organismal energetics and their relationship to whole organisms' energetics, health, and aging, and 2) provide quantitative, state-of-the-art technologies and novel methodologies in the assessment and analysis of bioenergetics to the geroscience community at large. In pursuit of these objectives, we will continue to provide three Research Cores. 1) The Comparative Organismal Energetics Core (a.k.a. Organismal Core) will provide expertise and cutting-edge instruction and methodology for determining complete whole-animal energy balance (intake, assimilation, and expenditure) and body composition, including regional distribution of white and brown adipose tissue, in living animals of various species, including worms, flies, fish, mice, or other mammals, under diverse temperature or activity regimes. 2) The Comparative Mitochondrial Health Assessment Core (a.k.a. Mitometabolism Core) will provide integrated, quantitative mitochondrial functional analysis at the level of the organelle, cell, or tissue for both traditional and emerging animal models, including targeted metabolomics, assessment of mitophagy, and oxidative stress. Mitochondrial-nuclear exchange models also will be available to enable experiments that evaluate the contribution of mtDNA variation to bioenergetics. 3) The Comparative Data Analytics Core (a.k.a. Analytics Core) will provide innovative analytic approaches to data sets linking comparative energetics to organismal health and longevity. With these Research Cores plus the Administrative Program Enrichment Core (Admin Core) and Research Development Core (RDC), we aim to: 1) facilitate hypothesis-driven research and leverage these technologies into new projects, interactions, and collaborations nationwide in basic aging research; 2) foster meaningful novel interactions among investigators within UAB and across the region and country; and 3) provide resources, education, training, and direction to junior investigators through the intellectual resources and research infrastructure the Center will develop.