Comparison of POLG mouse model with naturally aged rat model Jun Shi, Jascha Parkington, Sherry Chin, Tracee Kamunya, Samuel Cadena, Chikwendu Ibebunjo Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA
The mtDNA mutator mouse, POLG mouse, harboring a point mutation in the proofreading exonuclease activity of mitochondrial polymerase γ, exhibits accelerated aging phenotype. We compared POLG mice and 23-month-old rats to see whether underlying molecular signatures are similar in these two aging models. Mitochondrial electron transport chain complex activities, mtDNA copy number and mitochondrial protein expression from gastrocnemius muscles of POLG mice, sedentary or after 8-week voluntary wheel running (VWR), and aged rats were assayed. Activities of Complex I, III and IV decreased in POLG mice compared to WT. VWR failed to improve these, even though it significantly improved treadmill performance of POLG mice. mtDNA copy number did not change in POLG mice either. In contrast, mtDNA copy number and Complex II activity decreased a little in aged rats compared to young animals. However, Complex I and IV activities were not perturbed by age. The expression level of a panel of mitochondrial proteins was not significant different in POLG mice vs. WT and aged rats vs. young.
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