Long term rapamycin treatment improves mitochondrial DNA quality in aging mice

Experimental Gerontology
Jason H BielasJonathan Wanagat

Abstract

Age-induced mitochondrial DNA deletion mutations may underlie cell loss and tissue aging. Rapamycin extends mouse lifespan and modulates mitochondrial quality control. We hypothesized that reduced deletion mutation abundance may contribute to rapamycin's life extension effects. To test this hypothesis, genetically heterogeneous male and female mice were treated with rapamycin, compounded in chow at 14 or 42 ppm, from 9 months to 22 months of age. Mice under a 40% dietary restriction were included as a control known to protect mtDNA quality. To determine if chronic rapamycin treatment affects mitochondrial DNA quality, we assayed mtDNA deletion frequency and electron transport chain deficient fiber abundances in mouse quadriceps muscle. 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 treatmen...Continue Reading

Citations

Nov 13, 2018·Journal of Cellular Physiology·Farzaneh G TahrirKamel Khalili
Sep 24, 2020·Aging Clinical and Experimental Research·Allen HerbstJonathan Wanagat
Nov 7, 2019·Oxidative Medicine and Cellular Longevity·Yabing Xiong, Lili Zhou
Oct 11, 2020·GeroScience·Ramasamy SelvaraniArlan Richardson
Aug 16, 2019·Ageing Research Reviews·Mansour AkbariVilhelm A Bohr
Feb 23, 2021·Oncotarget·Mikhail V Blagosklonny
Jul 18, 2020·Current Pharmaceutical Design·Wheeler TorresJoselyn Rojas-Quintero

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