Project Summary – Comparative Mitochondrial Health Assessment Core The maintenance of normal mitochondrial bioenergetics and metabolism is essential for healthy aging. Although bioenergetic metrics have been surveyed in a broad range of aging models, further integration of these parameters with mitochondrial quality-control mechanisms and mitochondrial genetics is necessary for a better understanding of healthy aging. We will extend the new concept of bioenergetic health we have formulated in the previous funding period for age-related research. In the Comparative Mitochondrial Health Assessment Core (Mitometabolism Core) both state-of-the-art and established techniques in bioenergetics/metabolism, mitochondrial genetics, mitochondrial dynamics/mitophagy, and redox biology will be offered. State-of-the-art experimental design and protocols for assessing cellular bioenergetics in various live and frozen cells/tissues/organisms of aging models can be achieved. Mitochondrial dynamics and mitophagy have been shown to be essential for healthy lifespan, and deficiencies of these lead to accumulation of dysfunctional mitochondria. The Core will provide scientific and technical assistance to measure these parameters of mitochondrial quality control. The mitochondrial nuclear exchange (MNX) mice will be offered to the aging community to allow the contribution of specific mitochondrial DNA sequences to the process of aging to be assessed independent of the nuclear contribution. Services to be provided to NIA regular and supported members and pilot and feasibility grant awardees are: 1.) Molecular energetics analysis, including cellular, tissue, and small organism measurements and including approaches we have pioneered in spheroid-like cell structures and complex multi-cellular structures such as pancreatic islets, vessel segments and adipose tissue, and complementing approaches with targeted metabolomics. Novel techniques of assessing frozen tissues will vastly expand our ability to work with investigators outside UAB. 2.) State-of-the- art technologies to enable comparative mitophagy and mitochondrial dynamics, keys to mitochondrial health, and the integration of mitochondrial quality control with bioenergetic parameters. This will be further strengthened by interactions with the Analytics Core. 3.) Mitochondrial nuclear exchange (MNX) models, haplotyping, and mtDAMP measurements to test the unique contribution of mtDNA sequences to bioenergetics and the response to age-related disease. 4.) Virtual and wet lab workshop educational programs, as well as consultations.