Longevity Of Flies Research Articles

Neuroprotective Effect of farnesol against Rotenone Induced Parkinson’s Disease in Drosophila melanogaster

The aim of this study is to evaluate the neuroprotective role of farnesol against rotenone induced neurotoxicity in Drosophila melanogaster by survival rate study, negative geotaxis assay and estimation of in vivo antioxidant parameters. To induce neurotoxicity in flies, 500µmol of rotenone was used. After successful induction the flies were treated with 300 µmol and 600 µmol of farnesol for the duration of experimental period. The survival rate study was carried out to estimate the effect of farnesol on longevity of flies and negative geotaxis assay was carried out to determine the effect of farnesol on locomotor function of flies. The results indicated that 300 µmol and 600 µmol of farnesol extended the longevity and locomotor functions of the flies in a dose dependent manner. The in vivo antioxidant studies revealed that farnesol increased the activity of catalase and SOD and decreased lipid peroxidation. Based on the effect of farnesol on survival rate, longevity assay and antioxidant assay, we conclude that farnesol might possess significant neuroprotective property.

The effect of the sugar metabolism on Leishmania infantum promastigotes inside the gut of Lutzomyia longipalpis: A sweet relationship?

It is well-known that Leishmania parasites can alter the behavior of the sand fly vector in order to increase their transmission potential. However, little is known about the contribution of the infecting host's blood composition on subsequent sand fly infection and survival. This study focused on the host's glucose metabolism and the insulin/insulin-like growth factor 1 (IGF-1) pathway as both metabolic processes are known to impact vector-parasite interactions of other protozoa and insect species. The focus of this study was inspired by the observation that the glycemic levels in the blood of infected Syrian golden hamsters inversely correlated to splenic and hepatic parasite burdens. To evaluate the biological impact of these findings on further transmission, Lutzomyia longipalpis sand flies were infected with blood that was artificially supplemented with different physiological concentrations of several monosaccharides, insulin or IGF-1. Normoglycemic levels resulted in transiently higher parasite loads and faster appearance of metacyclics, whereas higher carbohydrate and insulin/IGF-1 levels favored sand fly survival. Although the recorded effects were modest or transient of nature, these observations support the concept that the host blood biochemistry may affect Leishmania transmission and sand fly longevity.

Enhanced germline stem cell longevity in Drosophila diapause

In many species including humans, aging reduces female fertility. Intriguingly, some animals preserve fertility longer under specific environmental conditions. For example, at low temperature and short day-length, Drosophila melanogaster enters a state called adult reproductive diapause. As in other stressful conditions, ovarian development arrests at the yolk uptake checkpoint; however, mechanisms underlying fertility preservation and post-diapause recovery are largely unknown. Here, we report that diapause causes more complete arrest than other stresses yet preserves greater recovery potential. During dormancy, germline stem cells (GSCs) incur DNA damage, activate p53 and Chk2, and divide less. Despite reduced niche signaling, germline precursor cells do not differentiate. GSCs adopt an atypical, suspended state connected to their daughters. Post-diapause recovery of niche signaling and resumption of division contribute to restoring GSCs. Mimicking one feature of quiescence, reduced juvenile hormone production, enhanced GSC longevity in non-diapausing flies. Thus, diapause mechanisms provide approaches to GSC longevity enhancement.

Inhibitor GSK690693 extends Drosophila lifespan via reduce AKT signaling pathway

Aging is a process involving physiological changes that lead to the decline of biological functions of various tissues and organs of the body. Therefore, it is crucial to find anti-aging drugs that can intervene with the changes induced because of aging and slow down the degeneration of the biological functions. Among many signaling pathways linked with aging and aging-related diseases, PI3K-AKT signaling pathway has attracted major attention in aging biology. In this research paper, we have demonstrated that AKT inhibitor GSK690693 can extend lifespan in Drosophila irrespective of start of the treatment from the beginning of life or the mid-life. Effect of GSK690693 for lifespan extension has been primarily related to the improvements in oxidative resistance, intestinal integrity and increased autophagy, but not in physical activity or starvation resistance. Furthermore, GSK690693 treatment reduced the activation of AKT and ERK, consequently activating FOXO, GSK-3β and apoptosis to modulate longevity of flies. Remarkably, GSK690693 did not induce hyperglycemia after treatment. The results indicate that GSK690693 may become an effective compound for anti-aging intervention.

Beneficial actions of esculentin-2CHa(GA30) on high sucrose-induced oxidative stress in Drosophila melanogaster

Hyperglycaemia-induced oxidative stress plays a critical role in the development of diabetes and its complications. This study investigated actions of esculentin-2CHa(GA30) on high sucrose-induced oxidative stress in adult Drosophila melanogaster. Adult flies were exposed to diets containing graded concentrations of sucrose in the presence or absence of esculentin-2CHa(GA30) (5.0–10 μmol/kg diet) for 7 days. Effects of high sucrose diet and/or esculentin-2CHa(GA30) on survival and longevity of flies, and markers of oxidative stress, antioxidant status and glucose were assessed. High-sucrose diet (15–30%) and esculentin-2CHa(GA30) (5–10 μmol/kg diet) enhanced the percentage of surviving flies by 33.5%–46.2% (P < 0.01) and 7.4%–26.9% (P < 0.01) respectively. Concentration-dependent reduction in total thiol (19.3–51.3%, P < 0.01), reduced glutathione (22.6–54.9%, P < 0.05–0.01), catalase activity (36.8–57.3%, P < 0.05–0.01) and elevated glucose concentration (1.8–2.9-fold, P < 0.001) were observed in high sucrose-fed flies. Esculentin-2CHa(GA30) alone did not affect levels of total thiol, reduced glutathione, glucose and catalase activity. Improved survival (1.2–1.3-fold, P < 0.05–0.01) and longevity (1.3-fold) were observed in flies treated with the peptide (5.0 and 7.5 μmol/kg diet). Feeding on sucrose and esculentin-2CHa(1–30) (5.0 and 7.0 μmol/kg diet) for 7 days increased total thiol (2 - 3-fold, P < 0.001) and reduced glutathione (1.6–1.8-fold, P < 0.05) levels. Reduced catalase activity (21.4–36.4%, P < 0.01) and reduced glucose level (38.6–49.4%, P < 0.01) were observed in peptide-treated flies. Esculentin-2CHa(1–30) inhibited sucrose-induced generation of hydrogen peroxide (7.5–13.7%, P < 0.05) and nitric oxide (22.3–42.9%, P < 0.01) in adult flies. Overall, findings from this study offered further insights into the anti-oxidative properties of esculentin-2CHa(GA30).

Enhancing mask activity in dopaminergic neurons extends lifespan in flies.

Dopaminergic neurons (DANs) are essential modulators for brain functions involving memory formation, reward processing, and decision‐making. Here I demonstrate a novel and important function of the DANs in regulating aging and longevity. Overexpressing the putative scaffolding protein Mask in two small groups of DANs in flies can significantly extend the lifespan in flies and sustain adult locomotor and fecundity at old ages. This Mask‐induced beneficial effect requires dopaminergic transmission but cannot be recapitulated by elevating dopamine production alone in the DANs. Independent activation of Gαs in the same two groups of DANs via the drug‐inducible DREADD system also extends fly lifespan, further indicating the connection of specific DANs to aging control. The Mask‐induced lifespan extension appears to depend on the function of Mask to regulate microtubule (MT) stability. A structure–function analysis demonstrated that the ankyrin repeats domain in the Mask protein is both necessary for regulating MT stability (when expressed in muscles and motor neurons) and sufficient to prolong longevity (when expressed in the two groups of DANs). Furthermore, DAN‐specific overexpression of Unc‐104 or knockdown of p150Glued, two independent interventions previously shown to impact MT dynamics, also extends lifespan in flies. Together, these data demonstrated a novel DANs‐dependent mechanism that, upon the tuning of their MT dynamics, modulates systemic aging and longevity in flies.

Moderate Red Wine Consumption Increases the Expression of Longevity-Associated Genes in Controlled Human Populations and Extends Lifespan in Drosophila melanogaster.

The beneficial effects of moderate red wine consumption on cardiovascular health are well known. The composition of red wine includes several compounds, such as the phytoestrogen resveratrol, that exert these beneficial effects, although not all the mechanisms by which they act are known. Our aim was to study the effect of red wine consumption on longevity-related genes in controlled human populations, such as cloistered nuns. We found that the expression of catalase, manganese-superoxide dismutase, Sirt1, and p53 was increased in peripheral blood mononuclear cells after 14 days of moderate red wine consumption. This increase was accompanied by an enhanced metabolic wellness: fatty acids, cholesterol, branched chain amino acids (isoleucine and leucine), ketone bodies (acetoacetate), bacterial co-metabolites (trimethylamine), and cellular antioxidants (taurine) contributed to a change in metabolic profile after moderate red wine consumption by the nuns. No serious unwanted side effects were observed. Finally, we tested the effect of moderate red wine consumption on longevity in a controlled animal population, such as D. melanogaster, and found that it increased average life span by 7%. In conclusion, moderate red wine consumption increases the expression of key longevity-related genes and improves metabolic health in humans and increases longevity in flies.

Edible Mushroom Protein Content and Antioxidant Capacity Increase the Longevity of Anastrepha ludens Fruit Flies.

This study aimed to determine the effect of the protein and antioxidant contents of edible mushrooms on the longevity of the fruit fly (Anastrepha ludens). The contents of protein (Bradford assay), antioxidants (DPPH and ABTS assays), total phenols, and flavonoids in nine strains of different edible mushroom species were determined. Freeze-dried and finely ground complete mushroom fruiting bodies were used to feed the flies, with a concentration of 0.5% in the diet. Male and female fruit flies, both fertile and sterile, were used in this study. Two controls were used: the standard fly diet and a diet supplemented with cinnamon as a food rich in antioxidants. Differences in protein and antioxidant contents were found among the evaluated strains. Differences were also observed in the responses of female and male flies as well as between the responses of fertile and sterile flies. Overall, the sterile flies lived longer. The addition of mushrooms in the diet resulted in greater longevity than in the controls. The use of sterile flies allowed observation of the effect of proteins and antioxidants on reproduction and the subsequent effect of reproduction on longevity.

Antioxidant Blend of Curcumin and Broccoli Seed Extract Exhibits Protective Effect on Neurodegeneration and Promotes Drosophila Lifespan.

Antioxidants and related compounds are anti-inflammatory and exhibit great potential in promoting human health. They are also often considered to be important elements in the process of neurodegeneration. Here we describe a antioxidant blend of Curcumin and Broccoli Seed Extract (BSE). Flies treated with the blend exhibit extended lifespan. RNA-seq analysis of samples from adult fly brains reveals a wide array of new genes with differential expression upon treatment with the blend. Interestingly, abolishing expression of some of the identified genes in dopaminergic (DA) neurons does not affect DA neuron number. Taken together, our findings reveal an antioxidant blend that promotes fly longevity and exhibits protective effect over neurodegeneration, demonstrating the importance of antioxidants in health and pathology.

The Effects of INDY on Fly Metabolism

The Indy (I’m not dead yet) gene encodes a plasma membrane citrate transporter in Drosophila. INDY reduction affects metabolism and extends longevity of flies and worms. In flies, INDY is predominantly expressed in the midgut, fat body and oenocytes, tissues with a key role in metabolism. We hypothesize that INDY reduction in the midgut regulates citrate levels leading to metabolic changes that preserve intestinal stem cell (ISC) homeostasis and slows aging by modifying Insulin/Insulin-like signaling (IIS), which is a key nutrient sensing pathway. Our second goal was to examine the role of JAK/STAT signaling pathway, which activates epithelial renewal in the gut, in response to aging-related stressors. We hypothesize that Indy reduction has effects on the microbiome, preventing bacterial overgrowth and altering community diversity, leading to extended longevity in a JAK/STAT-mediated fashion. Our data suggest that effects of Indy reduction is mediated by reduced IIS and JAK/STAT pathways

Disruption of duplicated yellow genes in Bactrocera tryoni modifies pigmentation colouration and impacts behaviour

Irradiated Queensland fruit flies (Bactrocera tryoni) used in Sterile Insect Technique (SIT) programmes are marked with fluorescent dyes to distinguish them from wild flies when recaptured in monitoring traps. However, coating sterile pupae with powdered dyes can reduce emergence rates and fly quality and can sometimes produce insufficiently certain discrimination through inadequate coating or because the dye is transferred to wild flies through contact. Here we created a phenotypically distinct B. tryoni strain that lacks typical melanisation patterns through CRISPR/Cas9-mediated mutagenesis of tandemly duplicated yellow-y genes and then assessed effects of this visible trait on fly performance. Recessive mutations are only required in one of these copies to restrict melanisation and generate a phenotype clearly distinguished from wild type. The yellow strain showed significant declines in eclosion rates and in the percentage of fliers directly after emergence. Locomotor activity was greater in the yellow strain, and these mutations did not generally affect mating probability, copula latency, or copula duration. The longevity of yellow flies was approximately 10 days shorter than wild-type flies in both sexes. Overall, replacing dyes with yellow body marker for SIT can simplify production, eliminate a step that is known to reduce fly quality, remove potentially hazardous dyes from production, enable accurate discrimination from wild flies, and improve cost-effectiveness; however, direct comparisons of the decrements in performance associated with dyes on mass-reared wild-type flies and disruption of yellow-y genes are now required to determine the relative suitability of these marking methods for B. tryoni SIT.

Moringa oleifera Leaf Extract Extends Lifespan and Ameliorate HAART Drug-Induced Locomotor, Reproductive, and Antioxidant Deficits in Drosophila melanogaster

Aim: To evaluate the longevity and ameliorative activities of Moringa oleifera leaf (MOL) extract against some HAART drug-induced toxicities in Drosophila melanogaster.&#x0D; Materials and Methods: The research was conducted at the Drosophila laboratory, Africa Centre of Excellence in phytomedicine Research and Development (ACEPRD), University of Jos-Nigeria, between August 2019 - March 2020. D. melanogaster (1-3 day) were first exposed for life to different concentrations of MOL (50 – 500 mg) or 25 mM Ascorbic acid or 1000 µL distilled water to determine longevity. Secondly, flies were fed on 46.56 mg of HAART drugs (Efavirenz-based or Dolutegravir-based) alone or supplemented with MOL 250 mg or 500 mg per 10 g fly food in five replicates for seven days. Afterward, longevity, fecundity, and negative geotaxis were evaluated. Also, activities of Superoxide dismutase, Catalase, as well as Malondialdehyde content as biomarkers of oxidative stress were evaluated using whole fly homogenate. Statistical significance was taken at P&lt;0.05 or (P&lt;0.006) (Bonferroni adjusted P-value for multiple curve comparisons. &#x0D; Results: The MOL extract significantly (P&lt;0.001) increased fly longevity compared to control groups. Similarly, supplementation with 500 mg MOL extracts significantly (P&lt;0.05) ameliorate HAART drug-induced deficits in climbing ability, fecundity, SOD, and CAT activities as well as MDA content compared to groups exposed to HAART drugs alone respectively.&#x0D; Conclusion: The results suggest that M. oleifera leaf extract extends lifespan and ameliorate HAART drug-induced toxicities via its antioxidant activities. This was supported by improved locomotor and reproductive decline, and restoration of the deficits in the biomarkers of oxidative stress (SOD, CAT, and MDA) in D. melanogaster.

Differential side-effects of Bacillus thuringiensis bioinsecticide on non-target Drosophila flies

Bioinsecticides based on Bacillus thuringiensis (Bt) spores and toxins are increasingly popular alternative solutions to control insect pests, with potential impact of their accumulation in the environment on non-target organisms. Here, we tested the effects of chronic exposure to commercial Bt formulations (Bt var. kurstaki and israelensis) on eight non-target Drosophila species present in Bt-treated areas, including D. melanogaster (four strains). Doses up to those recommended for field application (~ 106 Colony Forming Unit (CFU)/g fly medium) did not impact fly development, while no fly emerged at ≥ 1000-fold this dose. Doses between 10- to 100-fold the recommended one increased developmental time and decreased adult emergence rates in a dose-dependent manner, with species-and strain-specific effect amplitudes. Focusing on D. melanogaster, development alterations were due to instar-dependent larval mortality, and the longevity and offspring number of adult flies exposed to bioinsecticide throughout their development were moderately influenced. Our data also suggest a synergy between the formulation compounds (spores, cleaved toxins, additives) might induce the bioinsecticide effects on larval development. Although recommended doses had no impact on non-target Drosophila species, misuse or local environmental accumulation of Bt bioinsecticides could have side-effects on fly populations with potential implications for their associated communities.

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

ABSTRACTSleep 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.

Lactate dehydrogenase expression modulates longevity and neurodegeneration in Drosophila melanogaster.

Lactate dehydrogenase (LDH) catalyzes the conversion of glycolysis-derived pyruvate to lactate. Lactate has been shown to play key roles in brain energetics and memory formation. However, lactate levels are elevated in aging and Alzheimer’s disease patients, and it is not clear whether lactate plays protective or detrimental roles in these contexts. Here we show that Ldh transcript levels are elevated and cycle with diurnal rhythm in the heads of aged flies and this is associated with increased LDH protein, enzyme activity, and lactate concentrations. To understand the biological significance of increased Ldh gene expression, we genetically manipulated Ldh levels in adult neurons or glia. Overexpression of Ldh in both cell types caused a significant reduction in lifespan whereas Ldh down-regulation resulted in lifespan extension. Moreover, pan-neuronal overexpression of Ldh disrupted circadian locomotor activity rhythms and significantly increased brain neurodegeneration. In contrast, reduction of Ldh in neurons delayed age-dependent neurodegeneration. Thus, our unbiased genetic approach identified Ldh and lactate as potential modulators of aging and longevity in flies.

Roles of fresh and decomposed liver on aspects of reproduction of blowfly &lt;i&gt;Chrysomya chloropyga&lt;/i&gt; (wied.) (Diptera: Calliphoridae)

This study compared the effects of fresh and decomposed liver on aspects of reproduction of the blowfly, Chrysomya chloropyga to determine the possibility of multiple generations of the blowfly on a single cadaver. The total development time from egg to adult were 8.75 and 8.50 days in the flies fed on fresh and decomposed liver respectively and were not significantly different (p=0.58) from each other. The sex ratio (male: female) was 1:1 on both diets. There was a significant difference in the survival of adults fed fresh and decomposed liver (p=0.001, 0.001). There was no significant difference (p=0.362, 0.029) in the longevity of flies fed fresh and decomposed liver. Age at first egg laying on fresh and decomposed liver were 15.00 and 7.25 days respectively on fresh and decomposed liver. Fecundity of 175.6 eggs recorded in the flies fed on fresh liver was not significantly different (p=0.804) from that (200.8 eggs) of flies on decomposed liver. Mean weights of male and female flies maintained on both diet increased from the first day to tenth day only. However, it was not significantly different (p=0.130, 0.576) from each other throughout the period of exposure. Protein concentration was significantly higher in females fed fresh liver than those maintained on decomposed liver at ages 0 to 25 days. In conclusion, decomposed liver was as effective as fresh liver in supporting reproduction of the C. chloropyga with a better performance on decomposed liver. The study also demonstrated a strong indication for more than one generation of flies on a sizeable cadaver.&#x0D; Key Words: Blowfly, Chrysomya, Decomposition, Forensic entomology, Reproduction

EFVb-HAART Increases Mortality, Locomotor Deficits and Reduces Reproductive Capacity in Drosophila melanogaster

Aims: This study was designed to evaluate the effects of Efavirenz-based highly active antiretroviral therapy (EFVb-HAART, Efavirenz/Lamivudine/Tenofovir) with emphasis on survival, longevity, climbing ability, and reproductive capacity in D. melanogaster.&#x0D; Methods: The experiments were carried out at the Africa Center of Excellence in Phytomedicine Research and Development (ACEPRD), University of Jos, Nigeria between January 2017 and August 2018. D. melanogaster (both sexes) 1-4 days old were exposed to different concentrations of EFVb-HAART (range 10-1200 mg) in the fly food for initial 7 days to determine the LD50, then 5 day fly exposure to 93.11 mg, 46.56 mg, 23.28 mg or 11.64 mg for negative geotaxis assay, and acetylcholinesterase (AChE) activity. Furthermore, 28-day fly survival and longevity were determined. Statistical significance was presumed at P&lt; 0.05.&#x0D; Results: The LD50 of EFVb-HAART in D. melanogaster was 93.11 mg. The HAART exposed flies showed significantly (P&lt;0.001) increased mortality, significant (P&lt;0.001) decreased fly eclosion, acetylcholinesterse (AChE) activity and climbing ability compared to unexposed group at all experimental concentrations.&#x0D; Conclusion: The decreased 28-day survival, longevity, climbing ability and reproductive capacity at all experimental concentrations may be attributable to the deleterious effects of EFVb-HAART in D. melanogaster. Our findings suggest that long term use of EFVb-HAART by HIV patients may be associated with accelerated aging, decreased life expectancy, quality of life (due to possible neurotoxicity) and reproductive competence, as evidenced by increased mortality, reduced longevity, AChE activity, and 100% emergence failure respectively in D. melanogaster, and may require further study in humans. We recommend further research to expound the biochemical and molecular toxicodynamics of EFVb- HAART in D. melanogaster with the view of ameliorating same.

Eclosion and adult longevity traits ofRhagoletis tabellaria(Diptera: Tephritidae) andUtetes tabellariae(Hymenoptera: Braconidae) in the laboratory

AbstractEclosion times and rates ofRhagoletis tabellaria(Fitch) (Diptera: Tephritidae) and its parasitoid waspUtetes tabellariae(Fischer) (Hymenoptera: Braconidae) held at different chilling durations were determined in the laboratory. Adult fly and wasp longevity were also determined. Adult female and male flies fromR. tabellariapuparia chilled for 195 days at 4.8 °C and then held at 23.2 °C eclosed on average earlier thanU. tabellariaereared fromR. tabellariapuparia.Rhagoletis tabellariaalso eclosed significantly earlier from puparia chilled for 150 days than 120 days at 2.7 °C, butU. tabellariaeeclosion from the two treatments did not differ significantly.Rhagoletis tabellariaeclosion rates were greater with longer chill durations, butU. tabellariaeeclosion rates perR. tabellariapuparium did not differ among chill durations. NoR. tabellariaeclosed from nonchilled puparia held at 20–22 °C, but at least 18.8% of nonchilledU. tabellariaeeclosed. Female and maleR. tabellariaon average survived 52.1 and 83.3 days, respectively, while female and maleU. tabellariaesurvived 37.7 and 28.7 days, respectively. Results indicate diapause and developmental traits ofR. tabellariamay be more dependent on chilling durations and less flexible than those ofU. tabellariae, a wasp that appears adapted to flies in theR. tabellariaspecies complex.

Impact of mitonuclear interactions on life-history responses to diet.

Mitochondria are central to both energy metabolism and biosynthesis. Mitochondrial function could therefore influence resource allocation. Critically, mitochondrial function depends on interactions between proteins encoded by the mitochondrial and nuclear genomes. Severe incompatibilities between these genomes can have pervasive effects on both fitness and longevity. How milder deficits in mitochondrial function affect life-history trade-offs is less well understood. Here, we analyse how mitonuclear interactions affect the trade-off between fecundity and longevity in Drosophila melanogaster. We consider a panel of 10 different mitochondrial DNA haplotypes against two contrasting nuclear backgrounds (w1118 (WE) and Zim53 (ZIM)) in response to high-protein versus standard diet. We report strikingly different responses between the two nuclear backgrounds. WE females have higher fecundity and decreased longevity on high protein. ZIM females have much greater fecundity and shorter lifespan than WE flies on standard diet. High protein doubled their fecundity with no effect on longevity. Mitochondrial haplotype reflected nuclear life-history trade-offs, with a negative correlation between longevity and fecundity in WE flies and no correlation in ZIM flies. Mitonuclear interactions had substantial effects but did not reflect genetic distance between mitochondrial haplotypes. We conclude that mitonuclear interactions can have significant impact on life-history trade-offs, but their effects are not predictable by relatedness. This article is part of the theme issue 'Linking the mitochondrial genotype to phenotype: a complex endeavour'.

THE EFFECTS OF INDY ON FLY HEALTH

Indy (I’m not dead yet) gene encodes a plasma membrane transporter of Krebs’ cycle intermediates with highest affinity for citrate. Indy is the fly homolog of a mammalian mIndy (SLC13A5), which has the same physiological function. Reduced expression of the Indy gene extends longevity in fruit flies and worms. Genetic and pharmacological INDY reduction affects metabolism in flies, worms, mice, rats and non-human primates by affecting the levels of cytoplasmic citrate. In flies, INDY is predominantly expressed in the midgut, fat body and oenocytes, all tissues with a key role in metabolism. Our first goal was to examine our working hypothesis that INDY reduction in the midgut regulates citrate levels leading to metabolic changes that preserve intestinal stem cell (ISCs) homeostasis and slows aging by modifying Insulin/Insulin-like signaling (IIS). ISC homeostasis is vital for midgut homeostasis and contributes to health and longevity. We found that reduction of Indy preserves ISC homeostasis and intestinal integrity. The IIS is a key nutrient sensing pathway, which regulates growth, metabolism and longevity. Indy reduction is associated with decreased IIS activity. Our second goal was to examine the role of IIS in Indy mediated changes in ISC homeostasis and health. We found that at least some of INDY’s beneficial effects on fly health are mediated by the IIS.