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.
journal_name
Aging Celljournal_title
Aging cellauthors
Wang L,Davis SS,Borch Jensen M,Rodriguez-Fernandez IA,Apaydin C,Juhasz G,Gibson BW,Schilling B,Ramanathan A,Ghaemmaghami S,Jasper Hdoi
10.1111/acel.12849subject
Has Abstractpub_date
2019-06-01 00:00:00pages
e12849issue
3eissn
1474-9718issn
1474-9726journal_volume
18pub_type
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