JNK modifies neuronal metabolism to promote proteostasis and longevity.

Autor: Wang L; The Buck Institute for Research on Aging, Novato, California.; Genentech Inc., South San Francisco, California., Davis SS; The Buck Institute for Research on Aging, Novato, California., Borch Jensen M; The Buck Institute for Research on Aging, Novato, California., Rodriguez-Fernandez IA; The Buck Institute for Research on Aging, Novato, California., Apaydin C; The Buck Institute for Research on Aging, Novato, California., Juhasz G; Department of Anatomy, Cell and Developmental Biology, Eotvos Lorand University, Budapest, Hungary.; Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary., Gibson BW; The Buck Institute for Research on Aging, Novato, California., Schilling B; The Buck Institute for Research on Aging, Novato, California., Ramanathan A; The Buck Institute for Research on Aging, Novato, California., Ghaemmaghami S; Department of Biology, University of Rochester, Rochester, New York., Jasper H; The Buck Institute for Research on Aging, Novato, California.; Genentech Inc., South San Francisco, California.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2019 Jun; Vol. 18 (3), pp. e12849. Date of Electronic Publication: 2019 Feb 27.
DOI: 10.1111/acel.12849
Abstrakt: 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.
(© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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