Robust assembly of electron transfer chain in the brain of Naked Mole-Rat during aging

Abstract

Naked mole-rats (NMR, Heterocephalus glaber) are the longest-lived rodent species, with a maximum life span of more than 30 years. These long-lived mammals exhibit delayed aging phenotypes and resistance to age-related pathologies including neurodegeneration. Multiple regulatory pathways have been proposed for the anti-aging mechanisms in NMR including enhanced mitochondrial function and suppressed oxidative stress. In this study, we investigated the assembly of the electron transfer chain (ETC) which constitutes the structural base for the regulation of both oxidative phosphorylation and the production of reactive oxygen species (ROS), in brains from young and old NMR and C57BL/6 mice. While ETC assembly declined with aging in C57BL/6 mice, we found that NMR display a robust respiratory chain assembly at older ages in both males and females. Among them, individual complex IV and supercomplexes containing complex I and III or complex III and IV showed the most pronounced differences between two species. Our results indicate that a preserved robust assembly of ETC during aging contributes to enhanced mitochondrial oxidative phosphorylation and suppressed oxidative stress, which may contribute to the longevity and resistance to age-related pathologies in NMR.