Wang, L., Davis, S.S., Borch Jensen, M., Rodriguez-Fernandez, I.A., Apaydin, C., Juhasz, G., Gibson, B.W., Schilling, B., Ramanathan, A., Ghaemmaghami, S., Jasper, H. (2019). JNK modifies neuronal metabolism to promote proteostasis and longevity.  Aging Cell 18(3): e12849.

FBrf0242331

Research paper

Aging is associated with a progressive loss of tissue and metabolic homeostasis. This loss can be delayed by single-gene perturbations, increasing lifespan. How such perturbations affect metabolic and proteostatic networks to extend lifespan remains unclear. Here, we address this question by comprehensively characterizing age-related changes in protein turnover rates in the Drosophila brain, as well as changes in the neuronal metabolome, transcriptome, and carbon flux in long-lived animals with elevated Jun-N-terminal Kinase signaling. We find that these animals exhibit a delayed age-related decline in protein turnover rates, as well as decreased steady-state neuronal glucose-6-phosphate levels and elevated carbon flux into the pentose phosphate pathway due to the induction of glucose-6-phosphate dehydrogenase (G6PD). Over-expressing G6PD in neurons is sufficient to phenocopy these metabolic and proteostatic changes, as well as extend lifespan. Our study identifies a link between metabolic changes and improved proteostasis in neurons that contributes to the lifespan extension in long-lived mutants.

PMC6516429 (PMC) (EuropePMC)