JNK modifies neuronal metabolism to promote proteostasis and longevity

Aging Cell
Lifen WangHeinrich Jasper

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.

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Citations

Feb 19, 2020·Proteomics·Rishi Sharma, Arvind Ramanathan
May 28, 2019·Journal of Cellular Biochemistry·Bor Luen Tang
Oct 29, 2020·Genes & Genomics·Garbin Yu, Seogang Hyun
Jan 17, 2021·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Evelyn S VincowLeo J Pallanck
Oct 9, 2020·Ageing Research Reviews·Andrey A ParkhitkoNorbert Perrimon
Apr 20, 2021·Frontiers in Cardiovascular Medicine·Junbin YanBeihui He

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Methods Mentioned

BETA
RNAseq
transgenic
Profiler
protein assay
Assay

Software Mentioned

Adobe Illustrator
Tuxedo suite
ImageJ
Protein Prospector
mssplice
Microsoft excel 2007
Lifespan
Mass Profiler Professional
Analyst ®
DAVID

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