2.7. MOUSE MODELS TO EXPLAIN USEFUL MUTATIONS
Analyses of somatic mtDNA mutations in mouse post-mitotic tissues have revealed the same age-related increase as in humans. Analyses of mouse heart and brain mtDNA rearrangements using LX-PCR revealed primarily full-length mtDNA in young 2-4-month-old animals. However, in older 32-35-month animals, the heart and brain were found to have a large number of different mtDNAs deletions. The heart was also found to contain mtDNAs with extremely large deletions resulting in minicircles, a feature that appears to be unique to the heart (79).
Animals maintained for life on a calorie-restricted diet, the levels of these age-related aberrant mtDNA molecules were substantially reduced in the brain (79). Since dietary restriction is a well, established method, for extending the lifespan of rodents (80, 81), and has been associated with reduced ROS generation and damage to the mouse mitochondria (82), it follows that the accumulation of these altered mtDNAs is due to endogenous ROS damage