Vimar/RAP1GDS1 promotes acceleration of brain aging after flies and mice reach middle age

Abstract

AbstractBrain aging may accelerate after rodents reach middle age. However, the endogenous mediator that promotes this acceleration is unknown. We predict that the mediator may be expressed after an organism reaches middle age and dysregulates mitochondrial function. In the neurons of wild-typeDrosophila(flies), we observed that mitochondria were fragmented in aged flies, and this fragmentation was associated with mitochondrial calcium overload. In a previous study, we found that mitochondrial fragmentation induced by calcium overload was reversed by the loss ofVimar, which forms a complex with Miro. Interestingly,Vimarexpression was increased after the flies reached middle age. Overexpression ofVimarin neurons resulted in premature aging and mitochondrial calcium overload. In contrast, downregulation ofVimarin flies older than middle age promoted healthy aging. As the mouse homolog of Vimar,RAP1GDS1expression was found to be increased after mice reached middle age;RAP1GDS1-transgenic andRAP1GDS1-knockdown mice displayed similar responses to flies with overexpressed and reducedVimarexpression, respectively. This research provides genetic evidence of a conserved endogenous mediator that promotes accelerated brain aging.