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Tory Hagen
Principal Investigator, Linus Pauling Institute
Professor, Biochemistry and Biophysics
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RESEARCH:
Mitochondria convert unusable forms of energy into ATP but also produce high levels of free radicals as by-products in this process. We believe that the attendant oxidative damage caused by these free radicals eventually lead to mitochondrial dysfunction with age. This may result in energy deficits and the inability of cells to respond to environmental stresses. Ongoing research in our lab centers on understanding the (1) the extent of mitochondrial decay in aging (2) the consequences of such decline to cellular function and (3) whether dietary supplementation of key metabolites may improve mitochondrial function.
For these studies, we monitor mitochondrial function in mitotically active (liver) and post-mitotic (heart and brain) cells of young and old rats using techniques such as flow cytometry, confocal microscopy, centrifugal cell elutriation and oxygen consumption. These methods permit us to examine mitochondrial function within intact cells and allow usto determine the consequences of their decay to the cell as a whole. Results show that the majority of cells from old animals contain significant levels of dysfunctional mitochondria and we are now characterizing the underlying biochemical and molecular events that may have caused their impairment. We have also been successful in reversing certain aspects of mitochondrial decay by supplementing the diet with compounds such as carnitine or lipoic acid.
Other ongoing projects are designed to determine whether cells from old animals can adequately respond to environmental and toxicological insults that would require heightened ATP production to be successfully detoxified. It appears that because of mitochondrial decay, cells are much more susceptible to certain toxins or stresses with age. Again, feeding animals a diet supplemented with lipoic acid reverses this susceptibility. Overall, these studies are providing new insights as to the role that mitochondrial dysfunction plays in aging as well as identifying strategies to slow progression of metabolic decline evident with age.