Mitochondrial ATP Synthase Subunit d Interacts with TOR Signaling and Dietary Macronutrients to Modulate Proteostasis and Lifespan in Drosophila

ABSTRACT: Diet composition is a critical determinant of lifespan and nutrient imbalance is detrimental health. However, how nutrients interact with genetic factors to modulate lifespan remains elusive. We investigated how diet composition influences mitochondrial ATP synthase subunit d (ATPsyn-d) in modulating lifespan in Drosophila. ATPsyn-d knockdown extended lifespan in females fed low carbohydrate-to-protein (C:P) diets, but not the high C:P ratio diet. We also measured changes in the genome-wide expression profile induced by ATPsyn-d knockdown. Lifespan extension induced by ATPsyn-d knockdown was associated with increased resistance to oxidative stress, transcriptional changes in metabolism, proteostasis and immune genes, reduced protein damage and aggregation, and reduced phosphorylation of S6K and ERK in TOR and MAPK signaling, respectively. Our data reveal a link among diet, mitochondria, MAPK and TOR signaling in aging and stresses the importance of considering genetic background and diet composition in implementing interventions for promoting healthy aging.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE58778 | GEO | 2014/10/02

SECONDARY ACCESSION(S): PRJNA253478

REPOSITORIES: GEO