Diet composition is a critical determinant of lifespan, and nutrient imbalance is detrimental to 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. This extension 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 mitogen-activated protein kinase (MAPK) signaling, respectively. ATPsyn-d knockdown did not extend lifespan in females with reduced TOR signaling induced genetically by Tsc2 overexpression or pharmacologically by rapamycin. Our data reveal a link among diet, mitochondria, and MAPK and TOR signaling in aging and stresses the importance of considering genetic background and diet composition in implementing interventions for promoting healthy aging.
A mitochondrial ATP synthase subunit interacts with TOR signaling to modulate protein homeostasis and lifespan in Drosophila.
Xiaoping Sun,Charles T. Wheeler,J. Yolitz,Mara Laslo,T. Alberico,Yaning Sun,Q. Song,Sige Zou
Published 2014 in Cell Reports
ABSTRACT
PUBLICATION RECORD
- Publication year
2014
- Venue
Cell Reports
- Publication date
2014-09-25
- Fields of study
Biology, Medicine, Environmental Science
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- atpsyn-d
The mitochondrial ATP synthase subunit d targeted for knockdown in Drosophila females.
Aliases: ATP synthase subunit d, mitochondrial ATP synthase subunit d
- high c:p ratio diet
A diet with a higher carbohydrate-to-protein ratio used for comparison in the lifespan experiments.
Aliases: high carbohydrate-to-protein diet, high C:P diet
- low carbohydrate-to-protein (c:p) diet
A diet with a low carbohydrate-to-protein ratio used as a nutritional condition in the lifespan experiments.
Aliases: low C:P diet, low C:P diets
- oxidative stress resistance
The ability of flies to withstand oxidative stress, assessed as a physiological outcome after ATPsyn-d knockdown.
Aliases: resistance to oxidative stress
- protein homeostasis
The balance of protein damage, aggregation, and maintenance processes examined in the flies.
Aliases: proteostasis
- tor signaling
The nutrient-sensing signaling pathway that was evaluated through changes in downstream phosphorylation in the flies.
Aliases: Target of Rapamycin signaling, mTOR signaling
- tsc2 overexpression
A genetic manipulation used to reduce TOR signaling in the flies.
Aliases: Tsc2 OE
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