Meeting Abstract
S2.9 Monday, Jan. 4 Skeletal muscle mitochondrial metabolism in three rodent species with disparate longevity SHI, Yun; LIU, YuHong; JERNIGAN, Amanda L; BHATTACHARYA, Arunabh; BUFFENSTEIN, Rochelle; AUSTAD, Steven N; VAN REMMEN, Holly *; University of Texas Health Science Center, San Antonio VANREMMEN@UTHSCSA.EDU
The oxidative stress hypothesis of aging predicts that long lived species might produce less reactive oxygen species (ROS), exhibit superior antioxidant defenses, and/or have low amount or slowed rate of oxidative damage accumulation. In this study we measured skeletal muscle mitochondrial metabolism in three rodent species with disparate longevities, the common laboratory mouse (Mus musculus, 4 years), the white-footed mouse (Peromyscus leucopus, 8 years) and the naked mole rat (Heterocephalus glaber, 30 years), to test the hypothesis that longer-lived species have lower ROS generation and more efficient ATP production. Compared to mitochondria isolated from M. musculus skeletal tissue from the two long-lived species generated lower levels of ROS [H2O2 and/or superoxide] and mitochondria from H. glaber show a reduced inactivation of aconitase activity. Surprisingly ATP production rate is lower in the species with intermediate longevity despite increased ATP synthase activity. Separation of mitochondrial oxidative phosphorylation complexes by blue native gels with subsequent in-gel enzymatic activity assays shows that both P. leucopus and H. glaber have reduced activity of Complex I compared with M. musculus, while Complex IV activity is reduced in H. glaber but increased in P. leucopus. Lower ROS generation and increased potential for ATP synthesis through elevated ATP synthase are consistent with increased longevity in P. leucopus and H. glaber. However, future studies will be conducted to determine whether these changes are specific to skeletal muscle mitochondria or similar in different tissues in each species. In addition, we will expand the comparison to include other species of similar body size and basal metabolic rate.
