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The fruit fly acetyltransferase Chameau promotes starvation resilience at the expense of longevity

ABSTRACT: Proteins involved in cellular metabolism and molecular regulation can extend lifespan in various organisms in the laboratory. However, any improvement in aging would only provide an evolutionary benefit if the organisms were able to survive under non-ideal conditions. We have previously shown that Drosophila melanogaster carrying a loss-of-function allele of the acetyltransferase chameau (chm) has an increased healthy lifespan when fed ad libitum. Here, we show that loss of chm and reduction of its activity results in a substantial reduction of weight and a decrease in starvation resistance. This phenotype is caused by failure to properly regulate the genes and proteins required for energy storage and expenditure. The previously observed increase in survival time thus comes with the inability to prepare for and cope with nutrient stress. As the ability to survive in environments with restricted food availability is likely a stronger evolutionary driver than the ability to live a long life, chm is still present in the organism's genome despite its apparent negative effect on lifespan.

SUBMITTER: Anuroop Venkateswaran Venkatasubramani

PROVIDER: S-SCDT-10_15252-EMBR_202357023 | biostudies-other |

REPOSITORIES: biostudies-other

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The fruit fly acetyltransferase chameau promotes starvation resilience at the expense of longevity.

Project description:Proteins involved in cellular metabolism and molecular regulation can extend lifespan of various organisms in the laboratory. However, any improvement in aging would only provide an evolutionary benefit if the organisms were able to survive under non-ideal conditions. We have previously shown that Drosophila melanogaster carrying a loss-of-function allele of the acetyltransferase chameau (chm) has an increased healthy lifespan when fed ad libitum. Here, we show that loss of chm and reduction in its activity results in a substantial reduction in weight and a decrease in starvation resistance. This phenotype is caused by failure to properly regulate the genes and proteins required for energy storage and expenditure. The previously observed increase in survival time thus comes with the inability to prepare for and cope with nutrient stress. As the ability to survive in environments with restricted food availability is likely a stronger evolutionary driver than the ability to live a long life, chm is still present in the organism's genome despite its apparent negative effect on lifespan.

| S-EPMC10561354 | biostudies-literature

The fruit fly acetyltransferase chameau promotes starvation resilience at the expense of longevity

Project description:Proteins involved in cellular metabolism and molecular regulation can extend lifespan in various organisms in the laboratory. However, any improvement in aging would only provide an evolutionary benefit if the organisms were able to survive under non-ideal conditions. We have previously shown that Drosophila melanogaster carrying a loss of function allele of the acetyltransferase chameau (chm) has an increased healthy life span when fed ad libitum. Here, we show that loss of chm and a reduction of its activity result in a substantial reduction of weight and a decrease in starvation resistance. This phenotype is caused by a failure to properly regulate the genes and proteins required for energy storage and expenditure. The previously observed increase in survival time thus comes with the inability to prepare for and cope with nutrient stress. As the ability survive in environments with restricted food availability is likely a stronger evolutionary driver than the ability to live a long life, chm is still present in the organism’s genome despite its apparent negative effect on lifespan.

2023-08-21 | GSE211042 | GEO

The fruit fly acetyltransferase chameau promotes starvation resilience at the expense of longevity

Project description:The fruit fly acetyltransferase chameau promotes starvation resilience at the expense of longevity

| PRJNA868729 | ENA

The Drosophila acetyltransferase chameau (chm) promotes starvation resilience at the expense of a shortened life span

Project description:Proteins involved in cellular metabolism and molecular regulation have been shown to extend lifespan in various laboratory organisms. However, for any improvement in aging to confer an evolutionary benefit, organisms must also be able to survive under non-ideal conditions. Earlier, we discovered that the loss of chm function and reduced activity resulted in several notable effects. Firstly, flies with a loss-of-function allele of chm exhibited an extended healthy lifespan when provided with an unrestricted food supply, indicating that chm plays a role in lifespan regulation. In this study, we demonstrate that these flies also experience a significant reduction in weight and decreased starvation resistance compared to flies with normal chm function. Furthermore, based on observations from transcriptomic, proteomic, and acetylome data, we hypothesize that chm is important for regulating metabolism in Drosophila, particularly in energy storage and utilization. Moreover, we demonstrate that reduced chm activity affects carbohydrate metabolism in flies at the basal level and during changes in nutrient status. In summary, this study suggests that chm is also required for starvation resilience by regulating carbohydrate metabolism, and the previously observed increase in survival time likely accompanies the inability to prepare for and cope with nutrient stress. Finally, as the ability to adapt and survive in a food-restricted environment was likely a stronger evolutionary driver than the ability to live a long life, chm is still present in the organism's genome despite its apparent deleterious effect on lifespan.

2023-09-05 | PXD042471 | Pride

fruit fly

Project description:Phylogenomic analyses of the genus Drosophila reveals genomic signals of climate adaptation

| PRJNA736147 | ENA

Longevity-fertility trade-offs in the tephritid fruit fly, Anastrepha ludens, across dietary-restriction gradients.

Project description:Although it is widely known that dietary restriction (DR) not only extends the longevity of a wide range of species but also reduces their reproductive output, the interrelationship of DR, longevity extension and reproduction is not well understood in any organism. Here we address the question: 'Under what nutritional conditions do the longevity-enhancing effects resulting from food restriction either counteract, complement or reinforce the mortality costs of reproduction? To answer this question we designed a fine-grained DR study involving 4800 individuals of the tephritid fruit fly, Anastrepha ludens, in which we measured sex-specific survival and daily reproduction in females in each of 20 different treatments (sugar : yeast ratios) plus 4 starvation controls. The database generated from this 3-year study consisted of approximately 100 000 life-days for each sex and 750 000 eggs distributed over the reproductive lives of 2400 females. The fertility and longevity-extending responses were used to create contour maps (X-Y grid) that show the demographic responses (Z-axis) across dietary gradients that range from complete starvation to both ad libitum sugar-only and ad libitum standard diet (3 : 1 sugar : yeast). The topographic perspectives reveal demographic equivalencies along nutritional gradients, differences in the graded responses of males and females, egg production costs that are sensitive to the interaction of food amounts and constituents, and orthogonal contours (equivalencies in longevity or reproduction) representing demographic thresholds related to both caloric content and sugar : yeast ratios. In general, the finding that lifespan and reproductive maxima occur at much different nutritional coordinates poses a major challenge for the use of food restriction (or a mimetic) in humans to improve health and extend longevity in humans.

| S-EPMC2574784 | biostudies-other

Sleep-length differences are associated with altered longevity in the fruit fly Drosophila melanogaster.

Project description:Sleep deprivation has been shown to negatively impact health outcomes, leading to decreased immune responses, memory loss, increased activity of stress and inflammatory pathways, weight gain, and even behavioral changes. These observations suggest that sleep deprivation substantially interferes with important physiological functions, including metabolic pathways of energy utilization. Many of those phenotypes are correlated with age, suggesting that disrupted sleep may interfere with the aging process. However, little is known about how sleep disruption affects aging and longevity. Here, we investigate this relationship using eight representative fruit fly lines from the Sleep Inbred Panel (SIP). The SIP consists of 39 inbred lines that display extreme short- and long-sleep patterns, and constitutes a crucial Drosophila community resource for investigating the mechanisms of sleep regulation. Our data show that flies with short-sleep periods have ?16% longer life span, as well as reduced aging rate, compared to flies with long-sleep. In contrast, disrupting normal circadian rhythm reduces fly longevity. Short-sleep SIP flies moreover show slight metabolic differences to long-sleep lines, and to flies with disrupted circadian rhythm. These data suggest that the inbred SIP lines engage sleep mechanisms that are distinct from the circadian clock system.

| S-EPMC7520458 | biostudies-literature

eIF4EHP promotes Ldh mRNA translation in and fruit fly adaptation to hypoxia

Project description:Hypoxia induces profound modifications in the gene expression program of eukaryotic cells due to lowered ATP supply resulting from the blockade of oxidative phosphorylation. One significant consequence of oxygen deprivation is the massive repression of protein synthesis, leaving a limited set of mRNAs to be translated. D. melanogaster is strongly resistant to oxygen fluctuations, however the mechanisms allowing specific mRNA to be translated in hypoxia are still unknown. Here, we show that Ldh mRNA encoding lactate dehydrogenase is highly translated in hypoxia by a mechanism involving a CA-rich motif present in its 3' untranslated region. Furthermore, we identified the cap-binding protein eIF4EHP as a main factor involved in 3'UTR-dependent translation under hypoxia. In accordance with this observation, we show that eIF4EHP is necessary for Drosophila development under low oxygen concentrations and contributes to Drosophila mobility after hypoxic challenge. Altogether, our data bring new insight into mechanisms contributing to LDH production and Drosophila adaptation to oxygen variations.

| S-SCDT-10_15252-EMBR_202256460 | biostudies-other

The NMDA Receptor Promotes Sleep in the Fruit Fly, Drosophila melanogaster.

Project description:Considerable evidence indicates that sleep is essential for learning and memory. Drosophila melanogaster has emerged as a novel model for studying sleep. We previously found a short sleeper mutant, fumin (fmn), and identified its mutation in the dopamine transporter gene. We reported similarities in the molecular basis of sleep and arousal regulation between mammals and Drosophila. In aversive olfactory learning tasks, fmn mutants demonstrate defective memory retention, which suggests an association between sleep and memory. In an attempt to discover additional sleep related genes in Drosophila, we carried out a microarray analysis comparing mRNA expression in heads of fmn and control flies and found that 563 genes are differentially expressed. Next, using the pan-neuronal Gal4 driver elav-Gal4 and UAS-RNA interference (RNAi) to knockdown individual genes, we performed a functional screen. We found that knockdown of the NMDA type glutamate receptor channel gene (Nmdar1) (also known as dNR1) reduced sleep. The NMDA receptor (NMDAR) plays an important role in learning and memory both in Drosophila and mammals. The application of the NMDAR antagonist, MK-801, reduced sleep in control flies, but not in fmn. These results suggest that NMDAR promotes sleep regulation in Drosophila.

| S-EPMC4449117 | biostudies-literature

Transcriptional regulation of a chitinase gene by 20-hydroxyecdysone and starvation in the oriental fruit fly, Bactrocera dorsalis.

Project description:Insect chitinases are hydrolytic enzymes that are required for the degradation of glycosidic bonds of chitin. In this study, we identified and characterized a full-length cDNA of the chitinase gene (BdCht2) in the oriental fruit fly, Bactrocera dorsalis. The cDNA contains an open reading frame (ORF) of 1449 bp that encodes 483 amino acid residues and 126- and 296-bp non-coding regions at the 5'- and 3'-ends, respectively. The BdCht2 genome has four exons and three introns. The predicted molecular mass of the deduced BdCht2 is approximately 54.3 kDa, with an isoelectric point of 5.97. The 977 bp 5' flanking region was identified and the transcription factor binding sites were predicted. Bioinformatic analyses showed that the deduced amino acid sequence of BdCht2 had 34%-66% identity to that of chitinases identified in other insect species. Quantitative real-time PCR (qPCR) analyses indicated that BdCht2 was mainly expressed during the larval-pupal and pupal-adult transitions. The tissue-specific expression showed that the highest expression was in the integument, followed by the fat body and other tissues. Moreover, the expression of BdCht2 was upregulated significantly upon 20-hydroxyecdysone (20E) at different dose injections after 8 h compared to that of the control. Starvation also increased the expression of BdCht2 in the third-instar larvae and was suppressed again by re-feeding the insects. These results suggest that BdCht2 plays an important role in the molting process of B. dorsalis larvae and can be regulated by 20E.

| S-EPMC3821602 | biostudies-literature

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