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Abstract #1577

Flow-Metabolism Uncoupling & Extended Longevity as Observed with a Transgenic Mice Model

Ai-Ling Lin1, Peter T. Fox1, Holly Van Remmen2, Arlan G. Richardson2, Timothy Q. Duong1

1Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, United States; 2Barshop Institute for Logevity & Aging Studies, University of Texas Health Science Center, San Antonio, TX, United States

Increased lifespan is observed in mice with a mitochondrial mutation in an assembly protein (Surf1 knockout; Surf1-/-) for electron-transport-chain complex IV, which results in a reduction in the level of cytochrome c oxidase (COX). The pupose of the study, therefore, was to determine the basal flo-metabolism coupling relationship and the metabolic pathway in the Surf1-/- mice. Cerebral blood flow (CBF) and cerebral metabolic rate of glucose (CMRGlc) were measured with MRI and PET, respectively. The results showed that basal flow and metabolism were uncoupled in the Surf1-/- mice (the basal CBF of the Surf1-/- was observed 20% lower than that of the WT (P < 0.05), while the cerebral glucose uptake of the Surf1-/- mice increased 85% compared to the WT (P < 0.001). The data further demonstrated that the metabolic pathway of the Surf1-/- mice has shifted from oxidative to glycolytic metabolism (with decreased oxygen consumption, but with increased glucose uptake).