Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.11.145227v1?rss=1 Authors: Oka, M., Suzuki, E., Asada, A., Saito, T., Iijima, K. M., Ando, K. Abstract: Brain neurons play a central role in organismal aging, but underlying mechanisms are still unclear. Dietary restriction extends lifespan, suggesting that bioenergetic challenges may be beneficial. By contrast, cerebral blood flow and glycolysis decrease during aging, suggesting that brain neurons in aged animals experience an energy deficit. In this study, we analyzed age-associated changes in metabolic states in the brain neurons of Drosophila and how such changes affect aging. Using a genetically encoded fluorescent ATP biosensor, we show that ATP concentration decreases in the neuronal somata of the brain during aging. A decrease in glucose content, expression of glucose transporter and glycolytic enzymes, and mitochondrial quality correlated with the reduction in ATP concentration. The age-associated reduction in ATP concentration did not occur in brain neurons in which glycolysis was suppressed or glucose transporter was overexpressed to enhance glucose uptake, suggesting that lower glucose uptake and glycolysis underlies the reduction in ATP in aged neurons. In contrast, increasing the glucose uptake did not rescue age-associated mitochondrial damage and surpassed mitochondrial defects to maintain ATP levels. Furthermore, increasing neuronal glucose uptake suppressed age-dependent locomotor deficits and extended the life span, and life span extension was more prominent on the low-calorie diet. These results suggest that strategies aimed at increasing the neuronal uptake of glucose may further promote the beneficial effects of bioenergetic challenges on aging. Copy rights belong to original authors. Visit the link for more info