The fruit fly acetyltransferase chameau promotes starvation resilience at the expense of longevity
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PROVIDER: PRJNA868729 | ENA |
REPOSITORIES: ENA
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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
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
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 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.
| S-SCDT-10_15252-EMBR_202357023 | biostudies-other
Project description:A major goal of healthy aging is to prevent declining resilience and increasing frailty, which are associated with many chronic diseases and deterioration of stress response. We have successfully used loss-or-gain model of stress survival to quantify organismal resilience. As a proof of concept, this is demonstrated in C. elegans exposed to increasing oxidative stress induced by exogenous paraquat and with proteotoxic stress caused by endogenous polyQ and Aβ aggregation, respectively. Based on this, we reveal that abalone peptide AbaPep#07 (SETYELRK) not only promotes survival resilience against paraquat-induced oxidative stress but also confers protection against polyQ- or Aβ-mediated behavioral dysfunction in C. elegans, indicating its capacity against stress and neurodegeneration. Importantly, we further show that the peptide increases physical fitness of aged C. elegans and extends life span without compromise of growth and reproduction, demonstrating its cost-free prolongevity activity. Moreover, we reveal that the peptide induces differential expression of a number of genes, including innate immune, lipid metabolism and metabolic detoxification genes, which are associated with the SKN-1/Nrf transcription factor. Collectively, our findings demonstrate that the novel abalone cryptide AbaPep#07 increases stress survival resilience and cost-free longevity via SKN-1/Nrf-governed transcriptional reprogramming and provide an insight into the neuroprotective and health-promoting potential of cryptides as proteostasis regulators.
2023-11-06 | GSE246759 | GEO
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
Project description:The reversible posttranslational O-GlcNAc modification of serine or threonine residues of intracellular proteins is involved in many cellular events from signaling cascades to epigenetic and transcriptional regulation. O-GlcNAcylation is a conserved nutrient-dependent process involving two enzymes, O-GlcNAc Transferase (OGT) adding O-GlcNAc while O-GlcNAcase (OGA) removing it in a manner that’s protein and context dependent. O-GlcNAcylation is essential for epigenetic regulation of gene expression through its action on Polycomb and Trithorax and Compass complexes. However, the important role of O-GlcNAc on adult life and healthspan have been largely unexplored, mainly due the lack of available model systems. Cataloging the O-GlcNAc proteome has proven useful in understanding the biology of this modification in vivo. In this study, we leveraged a recently developed oga knockout fly mutant to identify the O-GlcNAcylated proteins in adult Drosophila melanogaster. The adult O-GlcNAc proteome revealed many proteins related to cell and organismal growth, development, differentiation, and epigenetics. We identified many O-GlcNAcylated proteins that serve a role in increased growth and decreased longevity, including HCF, SIN3A, LOLA, KISMET, ATX2, SHOT, and FOXO.
2021-04-26 | PXD025344 | Pride
Project description:Centenarians provide a unique lens through which to study longevity, healthy aging, and resiliency. Moreover, models of human aging and resilience to disease that allow for the testing of potential interventions are virtually non-existent. We obtained and characterized over 86 centenarian and offspring peripheral blood samples including those connected to functional independence data highlighting resistance to disability and cognitive impairment. Targeted methylation arrays were used in molecular aging clocks to compare and contrast differences between biological and chronological age in these specialized subjects. Isolated peripheral blood mononuclear cells (PBMCs) from 20 of these subjects were then successfully reprogrammed into high-quality induced pluripotent stem cell (iPSC) lines which were functionally characterized for pluripotency, genomic stability, and the ability to undergo directed differentiation. The result of this work is a one-of-a-kind resource for studies of human longevity and resilience that can fuel the discovery and validation of novel therapeutics for aging-related disease.
2024-09-25 | GSE276957 | GEO
Project description:Phylogenomic analyses of the genus Drosophila reveals genomic signals of climate adaptation
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Project description:Loss of function during ageing is accompanied by transcriptional drift, altering gene expression and contributing to a variety of age-related diseases. CREB-regulated transcriptional coactivators (CRTCs) have emerged as key regulators of gene expression that might be targeted to promote longevity. Here, we define the role of the Caenorhabditis elegans CRTC-1 in the epigenetic regulation of longevity. Endogenous CRTC-1 binds chromatin factors, including components of the COMPASS complex, which trimethylates lysine 4 on histone H3 (H3K4me3). CRISPR editing of endogenous CRTC-1 reveals that the CREB-binding domain in neurons is specifically required for H3K4me3-dependent longevity. However, this effect is independent of CREB but instead acts via the transcription factor AP-1. Strikingly, CRTC-1 also mediates global histone acetylation levels, and this acetylation is essential for H3K4me3-dependent longevity. Indeed, overexpression of an acetyltransferase enzyme is sufficient to promote longevity in wild-type worms. CRTCs, therefore, link energetics to longevity by critically fine-tuning histone acetylation and methylation to promote healthy ageing.
2023-08-02 | GSE239572 | GEO
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.
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