The maintenance of normal mitochondrial function varies between organisms as does their oxygen metabolism and response to pathophysiological stress. Although bioenergetic metrics have been surveyed in a broad range of aging models these parameters have yet to be integrated with measures of the control of mitochondrial quality and mitochondrial genetics. We have introduced the concept of Bioenergetic health in translational research and now plan to extend this to models of aging. In the Comparative Mitochondrial Health Assessment core both state of the art and established techniques in bioenergetics, mitochondrial genetics, autophagy and redox biology will be offered. The mechanisms controlling mitochondrial health involve mitochondrial genetics, mitochondrial-nuclear interaction and mitophagy. The novel models offered to the aging community will be the mitochondrial nuclear exchange (MNX) mice which have been pioneered at UAB. This allows the contribution of specific mitochondrial DNA sequences to the process of aging to be assessed independent of the nuclear contribution. State of the art experimental design, and protocols for assessing cellular bioenergetics in response to oxidative and metabolic stress will also be used. As autophagy and mitophagy have been shown to be essential for healthy lifespan, and insufficient autophagy contributes to accumulation of protein aggregates and dysfunctional mitochondria, indices of autophagic flux can be measured. An important aspect of the Core is extending these techniques to a variety of traditional species from yeast to mice, including both cryopreserved ?cell zoo? of fibroblasts from about 60 species of mammals and birds, a lot of these from species of ?exceptional biogerontological interest?, as well as live species that are either exceptionally long-lived or short-lived for their body size, such as the short-lived fish, Nothobranchius furzeri. Specifically, services will be provided to NIA Regular and Supported Members and pilot & feasibility grant awardees in: 1. Molecular energetics analysis including cellular, organelle and tissue measurements, 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 and oxygen electrodes. 2. Quantitative oxidative stress parameters to assess indices of redox changes including oxidized lipids, thiols and modified proteins. 3. Mitochondrial nuclear exchange (MNX) models, mtDNA damage and haplotyping to test the unique contribution of mtDNA sequences to bioenergetics and the resistance to metabolic and oxidative stress, with approaches available for both the traditional murine models and comparative models of aging used throughout the Center. 4. Autophagy and mitophagy assessments in the context of the pathobiology of oxidative stress and neurodegeneration will be extended to the models of aging. 5. Virtual and wet lab workshop educational programs.
| Xu, Ming; Pirtskhalava, Tamar; Farr, Joshua N et al. (2018) Senolytics improve physical function and increase lifespan in old age. Nat Med 24:1246-1256 |
| Chusyd, Daniella E; Brown, Janine L; Hambly, Catherine et al. (2018) Adiposity and Reproductive Cycling Status in Zoo African Elephants. Obesity (Silver Spring) 26:103-110 |
| Mao, Kai; Quipildor, Gabriela Farias; Tabrizian, Tahmineh et al. (2018) Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice. Nat Commun 9:2394 |
| Brown, Andrew W; Kaiser, Kathryn A; Allison, David B (2018) Issues with data and analyses: Errors, underlying themes, and potential solutions. Proc Natl Acad Sci U S A 115:2563-2570 |
| Fischer, Kathleen E; Riddle, Nicole C (2018) Sex Differences in Aging: Genomic Instability. J Gerontol A Biol Sci Med Sci 73:166-174 |
| Rangarajan, Sunad; Bone, Nathaniel B; Zmijewska, Anna A et al. (2018) Metformin reverses established lung fibrosis in a bleomycin model. Nat Med 24:1121-1127 |
| Gibbs, Victoria K; Schwartz, Tonia S; Johnson, Maria S et al. (2018) No Significant Effect of Maternal Perception of the Food Environment on Reproductive Success or Pup Outcomes in C57BL/6J Mice. Obesity (Silver Spring) 26:723-729 |
| Zhang, Jianhua; Culp, Matilda Lillian; Craver, Jason G et al. (2018) Mitochondrial function and autophagy: integrating proteotoxic, redox, and metabolic stress in Parkinson's disease. J Neurochem 144:691-709 |
| Gardinassi, Luiz G; Arévalo-Herrera, Myriam; Herrera, Sócrates et al. (2018) Integrative metabolomics and transcriptomics signatures of clinical tolerance to Plasmodium vivax reveal activation of innate cell immunity and T cell signaling. Redox Biol 17:158-170 |
| Austad, Steven N (2018) The Comparative Biology of Mitochondrial Function and the Rate of Aging. Integr Comp Biol 58:559-566 |
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