Open AccessJNK modifies neuronal metabolism to promote proteostasis and longevity
Author(s) -
Wang Lifen,
Davis Sonnet S.,
Borch Jensen Martin,
RodriguezFernandez Imilce A.,
Apaydin Cagsar,
Juhasz Gabor,
Gibson Bradford W.,
Schilling Birgit,
Ramanathan Arvind,
Ghaemmaghami Sina,
Jasper Heinrich
Publication year - 2019
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12849
Subject(s) - proteostasis , biology , phenocopy , metabolome , pentose phosphate pathway , longevity , transcriptome , microbiology and biotechnology , protein turnover , flux (metallurgy) , metabolism , phenotype , metabolic pathway , glycolysis , genetics , gene , biochemistry , metabolomics , bioinformatics , gene expression , protein biosynthesis , materials science , metallurgy
Abstract 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.