Long term rapamycin treatment improves mitochondrial DNA quality in aging mice

At 42 ppm rapamycin, we observed a 57% decrease in deletion frequency, a 2.8-fold decrease in ETC deficient fibers, and a 3.4-fold increase in the number of mice without electron transport chain deficient fibers. We observed a similar trend with the 14 ppm dose. DR significantly decreased ETC deficient fiber abundances with a trend toward lower mtDNA deletion frequency. The effects of rapamycin treatment on mitochondrial DNA quality were greatest in females at the highest dose. Rapamycin treatment at 14 ppm did not affect muscle mass or function. Dietary restriction also reduced deletion frequency and ETC deficient fibers. These data support the concept that the lifespan extending effects of rapamycin treatment result from enhanced mitochondrial DNA quality.