Lifespan Of Flies Research Articles

Monochromatic visible lights modulate the timing of pre-adult developmental traits in Drosophila melanogaster.

Light exposure impacts several aspects of Drosophila development including the establishment of circadian rhythms, neuroendocrine regulation, life-history traits, etc. Introduction of artificial lights in the environment has caused almost all animals to develop ecological and physiological adaptations. White light which comprises different lights of differing wavelengths shortens the lifespan in fruit flies Drosophila melanogaster. The wavelength-specific effects of white light on Drosophila development remains poorly understood. In this study, we show that different wavelengths of white light differentially modulate Drosophila development in all its concomitant stages when maintained in a 12-h light: 12-h dark photoperiod. We observed that exposure to different monochromatic lights significantly alters larval behaviours such as feeding rate and phototaxis that influence pre-adult development. Larvae grown under shorter wavelengths of light experienced an altered feeding rate. Similarly, larvae were found to avoid shorter wavelengths of light but were highly attracted to the longer wavelengths of light. Most of the developmental processes were greatly accelerated under the green light regime while in other light regimes, the effects were highly varied. Interestingly, pre-adult survivorship remained unaltered across all light regimes but light exposure was found to show its impact on sex determination. Our study for the first time reveals how different wavelengths of white light modulate Drosophila development which in the future might help in developing non-invasive therapies and effective pest measures.

Kaempferol counteracts toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in D. melanogaster: An implication of its mitoprotective activity

The current study aimed to investigate whether kaempferol (KMP), the major bioactive component of green leafy vegetables, could counteract the toxicity elicited by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Drosophila melanogaster or not. First, we performed a dose-response curve, where adult wild-type flies were fed on diet-containing different concentrations of KMP throughout their lifespan. Afterward, flies were fed on a diet containing MPTP (500 μM) and KMP (20 and 40 μM) for 7 days. The MPTP- fed flies presented a higher mortality rate, lower emergence rate, locomotor deficits, and disruption in circadian rhythm when compared to the control. MPTP exposure induced severe oxidative stress, which was marked by reduction in thiol content, overproduction of reactive species, lipid and protein oxidation, and disruption of enzymes of antioxidant and neurotransmission pathways. MPTP also compromised the mitochondrial dynamics and respiration of flies, affecting the electron transport chain, oxidative phosphorylation, and fusion/fission processes. Besides extending per se the lifespan of flies, KMP counteracted the toxic effects of MPTP on the circadian cycle, survival, climbing, and hatching rates. KMP was also effective in restoring the activities of acetylcholinesterase (AChE) and monoamine oxidase (MAO) enzymes, as well as in normalizing the levels of all oxidant/antioxidant markers disrupted in MPTP-fed flies. Indeed, KMP reestablished the mitochondrial functionality in MPTP- fed flies, restoring the electron transport system linked to mitochondrial complex I and II, and rescuing the mRNA transcription of genes associated with mitochondrial fusion and fission, namely OPA-1 (Optic atrophy 1) and DRP-1 (Dynamin related protein 1). Our results showed the efficacy of KMP in hindering the toxicity induced by MPTP in D. melanogaster and suggest that the mitoprotective action of flavonoid may be boosting its anti-parkinsonism activity in the model. Besides, the study showed that wild-type strains of D. melanogaster proved to be reproducible in vivo model to mimic parkinsonian phenotypes through exposure to the neurotoxin MPTP.

Structure characteristics of low molecular weight pectic polysaccharide and its anti-aging capability by modulating the intestinal homeostasis

Pectic polysaccharide has attracted increasing attention for their potential biological properties and applications in health industries. In this study, a low-molecular-weight pectic polysaccharide, POS4, was obtained from citrus peel. The structure of POS4 was preliminarily analyzed by gel-permeation chromatography, monosaccharide analysis, infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR). Results showed that the molecular weight of POS4 was 4.76 kDa and it was a galacturonic acid enriched pectic polysaccharide. The anti-aging activity in vivo showed that POS4 could notably prolong the average lifespan of fruit flies by suppressing the generation of reactive oxygen species (ROS). Further studies demonstrated that POS4 could enhance intestinal homeostasis by modulating gut microbiota in a positive way and regulating autophagy associated genes. Taken together, we proposed that galacturonic acid enriched low molecular weight pectic polysaccharide have great potential in the development of healthy foods such as anti-aging health care products.

Early life exercise training and inhibition of apoLpp mRNA expression to improve age-related arrhythmias and prolong the average lifespan in Drosophila melanogaster.

Cardiovascular disease (CVD) places a heavy burden on older patients and the global healthcare system. A large body of evidence suggests that exercise training is essential in preventing and treating cardiovascular disease, but the underlying mechanisms are not well understood. Here, we used the Drosophila melanogaster animal model to study the effects of early-life exercise training (Exercise) on the aging heart and lifespan. We found in flies that age-induced arrhythmias are conserved across different genetic backgrounds. The fat body is the primary source of circulating lipoproteins in flies. Inhibition of fat body apoLpp (Drosophila apoB homolog) demonstrated that low expression of apoLpp reduced the development of arrhythmias in aged flies but did not affect average lifespan. At the same time, exercise can also reduce the expression of apoLpp mRNA in aged flies and have a protective effect on the heart, which is similar to the inhibition of apoLpp mRNA. Although treatment of UAS-apoLppRNAi and exercise alone had no significant effect on lifespan, the combination of UAS-apoLppRNAi and exercise extended the average lifespan of flies. Therefore, we conclude that UAS-apoLppRNAi and exercise are sufficient to resist age-induced arrhythmias, which may be related to the decreased expression of apoLpp mRNA, and that UAS-apoLppRNAi and exercise have a combined effect on prolonging the average lifespan.

DNAGLU Extends Life Span and Promotes Fitness and Stress Resistance in Drosophila.

To identify new factors that promote longevity and healthy aging, we studied Drosophila CG13397, an ortholog of the human NAGLU gene, a lysosomal enzyme overexpressed in centenarians. We found that the overexpression of CG13397 (dNAGLU) ubiquitously, or tissue specifically, in the nervous system or fat body could extend fly life span. It also extended the life span of flies overexpressing human Aβ42, in a Drosophila Alzheimer's disease (AD) model. To investigate whether dNAGLU could influence health span, we analyzed the effect of its overexpression on AD flies and found that it improved the climbing ability and stress resistance, including desiccation and hunger, suggesting that dNAGLU improved fly health span. We found that the deposition of Aβ42 in the mushroom body, which is the fly central nervous system, was reduced, and the lysosomal activity in the intestine was increased in dNAGLU over-expressing flies. When NAGLU was overexpressed in human U251-APP cells, which expresses a mutant form of the Aβ-precursor protein (APP), APP-p.M671L, these cells exhibited stronger lysosomal activity and and enhanced expression of lysosomal pathway genes. The concentration of Aβ42 in the cell supernatant was reduced, and the growth arrest caused by APP expression was reversed, suggesting that NAGLU could play a wider role beyond its catalytic activity to enhance lysosomal activity. These results also suggest that NAGLU overexpression could be explored to promote healthy aging and to prevent the onset of neurodegenerative diseases, including AD.

Effects of Se-enriched Chrysanthemum morifolium on lifespan and antioxidant defense-related gene expression of Drosophila melanogaster model.

Chrysanthemum morifolium is a well-known edible medicinal plant in Asia and some other regions. Content of selenium in Se-enriched C. morifolium (SeCM) is significantly higher than that in traditional C. morifolium (non-Se-enriched C. morifolium, TCM). In order to understand health effects of SeCM, its chemical composition, lifespan-prolonging activities, and impacts on antioxidant defense-related gene expressions of model organism D. melanogaster were systematically studied. A total of eight phenols, including luteolin-7-O-glucoside, linarin, luteolin, apigenin, diosmetin, acacetin, 3-caffeoylquinic acid and 4,5-dicaffeoylquinic acid, were identified in SeCM extract. Compared with TCM, SeCM exhibited superior antioxidant properties. Intake of SeCM dramatically reduced malondialdehyde level and increased activities of endogenous antioxidant enzymes in fruit flies. SeCM was able to upregulate gene expressions of Cu/Zn-superoxide dismutase, Mn-superoxide dismutase and hydrogen peroxide catalase, and extend lifespans of fruit flies. Comparatively high antioxidant capacities and lifespan-prolonging activities of SeCM might be attributed to its abundant phenols and selenium, which probably ameliorated accumulation of free radicals and susceptibility to oxidative stress. These findings provide clues on further exploitation and utilization of Se-enriched C. morifolium. PRACTICAL APPLICATIONS: Chrysanthemum morifolium has been used for nutraceutical and curative purposes in China for thousands of years. Se-enriched C. morifolium typically contains more selenium than traditional C. morifolium, and is widely consumed in Asia and some other regions. Selenium is an essential micronutrient for humans, and selenium deficiency may result in several diseases such as myocardial infarction. SeCM is one of important selenium supplements. In this study, SeCM was found to upregulate gene expressions of Cu/Zn-superoxide dismutase, Mn-superoxide dismutase, and hydrogen peroxide catalase, and extend lifespans of experimental animals. These results provide supporting information for developing SeCM-based functional foods with distinct health benefits.

A circular RNA Edis-Relish-castor axis regulates neuronal development in Drosophila.

Circular RNAs (circRNAs) are a new group of noncoding/regulatory RNAs that are particularly abundant in the nervous system, however, their physiological functions are underexplored. Here we report that the brain-enriched circular RNA Edis (Ect4-derived immune suppressor) plays an essential role in neuronal development in Drosophila. We show that depletion of Edis in vivo causes defects in axonal projection patterns of mushroom body (MB) neurons in the brain, as well as impaired locomotor activity and shortened lifespan of adult flies. In addition, we find that the castor gene, which encodes a transcription factor involved in neurodevelopment, is upregulated in Edis knockdown neurons. Notably, castor overexpression phenocopies Edis knockdown, and reducing castor levels suppresses the neurodevelopmental phenotypes in Edis-depleted neurons. Furthermore, chromatin immunoprecipitation analysis reveals that the transcription factor Relish, which plays a key role in regulating innate immunity signaling, occupies a pair of sites at the castor promoter, and that both sites are required for optimal castor gene activation by either immune challenge or Edis depletion. Lastly, Relish mutation and/or depletion can rescue both the castor gene hyperactivation phenotype and neuronal defects in Edis knockdown animals. We conclude that the circular RNA Edis acts through Relish and castor to regulate neuronal development.

Human Alpha 1 Antitrypsin Suppresses NF-κB Activity and Extends Lifespan in Adult Drosophila.

Human alpha 1 antitrypsin (hAAT) is a multifunctional protein that has been shown to have anti-inflammatory and cellular protective properties. While previous studies demonstrated the antiaging potential of hAAT, the mechanism(s) underlying the antiaging effect remain elusive. In this study, we performed a detailed analysis of transcriptomic data that indicated that NF-κB-targeted genes and NF-κB-regulated pathways were selectively inhibited by hAAT treatment. We further showed that the first detectable impact of hAAT treatment was the inhibition of the nuclear activity of NF-κB. Subsequently, hAAT treatment suppressed the mRNA levels of NF-κB-targeted genes, as well as NF-κB itself (P65 and P50), in human senescent cells. Using Drosophila models, we further examined the impact of hAAT on locomotor activity and endurance. Finally, using an adult-specific promotor, we demonstrated that overexpression of hAAT in the late stage of life significantly extended the lifespan of transgenic flies. These results extend the current understanding of the anti-inflammatory function of hAAT.

Flos puerariae ameliorates the intestinal inflammation of Drosophila via modulating the Nrf2/Keap1, JAK-STAT and Wnt signaling.

Gut homeostasis is important for human health, and its disruption can lead to inflammatory bowel disease (IBD). Flos Puerariae is a herb with a wide variety of pharmacological activities including antioxidant, antidiabetic, antialcoholismic and anti-inflammatory properties. However, the role of Flos Puerariae on treating IBD remains obscure. Here, we employed Drosophila melanogaster as a model organism to investigate the protective effect of Flos Puerariae extract (FPE) against sodium dodecyl sulfate (SDS)-induced intestinal injury. Our data showed that FPE had no toxic effect in flies, and significantly extended lifespan in SDS-inflamed flies, reduced stem cell proliferation in the midgut, and maintained intestinal morphological integrity. Furthermore, FPE remarkably recused the altered expression level of genes and proteins in Nrf2/Keap1 signaling, JAK-STAT signaling and Wnt signaling pathways in gut of inflammation flies. Thus, FPE has a protective effect against intestinal injury possibly via increasing the Nrf2/keap1 pathway and suppressing the JAK-STAT and Wnt signaling pathways, which would have tremendous potential for treating IBD.

Regulation of sensory perception and motor abilities by brain-specific action of chromatin remodeling factor CHD1.

The ATP-dependent chromatin remodeling factor CHD1 (chromodomain-helicase-DNA binding protein 1) is involved in both the de novo assembly and the remodeling of chromatin. Recently, we discovered a crucial role of CHD1 in the incorporation of the histone variant H3.3 in the fly brain illustrated by widespread transcriptional upregulation and shortened lifespan in Chd1-mutant animals. Because many genes linked to sensory perception were dysregulated in Chd1-mutant heads, we studied the role of CHD1 in these processes. Here we show that Chd1-mutant flies have severe defects in their response behavior to olfactory and gustatory but not visual stimuli. Further analyses suggested that poor performance in gustatory response assays was caused by reduced motivation for foraging and feeding rather than defects in taste perception. Moreover, we show that shortened lifespan of Chd1-mutant flies is accompanied by indications of premature functional aging as suggested by defects in negative geotaxis and exploratory walking assays. The latter phenotype was rescued by neuronal re-expression of Chd1, while the olfactory defects were not. Interestingly, we found evidence for indirect regulation of the non-neuronal expression of odorant binding proteins (Obp) by neuronal expression of Chd1. Together, these results emphasize the crucial role of CHD1 activity controlling diverse neuronal processes thereby affecting healthy lifespan.

Age-dependent effects of blue light exposure on lifespan, neurodegeneration, and mitochondria physiology in Drosophila melanogaster

Blue light is a predominant component of light emitting devices (LEDs), which are increasingly present in our environment. There is already accumulating evidence that blue light exposure causes damage to retinal cells in vitro and in vivo; however, much less is known about potential effects of blue light on non-retinal cells. That blue light may be detrimental at the organismal level independent from retinal effect was recently shown by findings that it reduces lifespan in worms and also in flies with genetically ablated retinas. Here, we investigated the effects of blue light exposure across the fly lifespan and found that susceptibility to blue light stress is strongly age-dependent. The blue light of the same intensity and duration reduced survival and increased neurodegeneration more significantly in old flies than in young flies. These differences appear to be caused, at least in part, by impairments of mitochondrial respiratory function. We report that blue light significantly reduces the activity of Complex II in the electron transport system and decrease the biochemical activity of succinate dehydrogenase in both young and old flies. In addition, complex I and complex IV activities are reduced by age, as are ATP levels. We therefore propose that older flies are more sensitive to blue light because the light-induced mitochondrial damage potentiates the age-related impairments in energy metabolism that occurs even in darkness. Taken together, our results show that damaging effects of blue light at the organismal level are strongly age dependent and are associated with reduced activity of specific components of energy producing pathways in mitochondria.

Antiaging function of Chinese pond turtle (Chinemys reevesii) peptide through activation of the Nrf2/Keap1 signaling pathway and its structure-activity relationship.

Chinese pond turtle is a traditional nourishing food with high nutritional value and bioactivity and has been considered a dietary remedy for prolonging the lifespan since ancient times. However, only limited information about their effects on longevity is available. This study was performed to assess the antioxidant activities and antiaging potential of Chinese pond turtle peptide (CPTP) using Drosophila melanogaster model and uncover the possible mechanisms underlying the beneficial effects. CPTP exhibited excellent antioxidant capability in vitro with IC50 values of 3.31, 1.93, and 9.52 mg/ml for 1,1-diphenyl-2-pycryl-hydrazyl (DPPH), 2,2-azinobis (3-ethylbenzothiazo-line-6-sulfonic acid) diammonium salt (ABTS), and hydroxyl radical scavenging, respectively. In vivo, 0.8% of CPTP significantly extended the mean and median lifespan of female flies by 7.66 and 7.85%, followed by enhanced resistance to oxidative and heat stress. Besides, CPTP remarkably increased the antioxidant enzyme activities and diminished the peroxide product accumulation. Furthermore, CPTP upregulated the relative mRNA expression of antioxidant-related genes, including nuclear factor-erythroid-2-like 2 (Nrf2) and its downstream target genes, while downregulated the expression of Kelch-like ECH-associated protein 1 (Keap1). Taken together, CPTP displayed promising potential in both antioxidant and antiaging effects on flies by targeting the Nrf2/Keap1 pathway. Further peptide sequence determination revealed that 89.23% of peptides from the identified sequences in CPTP could exert potential inhibitory effects on Keap1. Among these peptides, ten representative peptide sequences could actively interact with the binding sites of Keap1-Nrf2 interaction through hydrogen bonds, van der Walls, hydrophobic interactions, and electrostatic interactions. Conclusively, CPTP could be utilized as health-promoting bioactive peptide with antioxidant and antiaging capacities.

Casein kinase 1δ/ε phosphorylates fused in sarcoma (FUS) and ameliorates FUS-mediated neurodegeneration

Aberrant cytoplasmic accumulation of an RNA-binding protein, fused in sarcoma (FUS), characterizes the neuropathology of subtypes of ALS and frontotemporal lobar degeneration, although the effects of post-translational modifications of FUS, especially phosphorylation, on its neurotoxicity have not been fully characterized. Here, we show that casein kinase 1δ (CK1δ) phosphorylates FUS at 10 serine/threonine residues in vitro using mass spectrometric analyses. We also show that phosphorylation by CK1δ or CK1ε significantly increased the solubility of FUS in human embryonic kidney 293 cells. In transgenic Drosophila that overexpress wt or P525L ALS-mutant human FUS in the retina or in neurons, we found coexpression of human CK1δ or its Drosophila isologue Dco in the photoreceptor neurons significantly ameliorated the observed retinal degeneration, and neuronal coexpression of human CK1δ extended fly life span. Taken together, our data suggest a novel regulatory mechanism of the assembly and toxicity of FUS through CK1δ/CK1ε-mediated phosphorylation, which could represent a potential therapeutic target in FUS proteinopathies.

Sodium Benzoate Delays the Development of Drosophila melanogaster Larvae and Alters Commensal Microbiota in Adult Flies.

Sodium benzoate (SB), the sodium salt of benzoic acid, is widely used as a preservative in foods and drinks. The toxicity of SB to the human body attracted people’s attention due to the excessive use of preservatives and the increased consumption of processed and fast foods in modern society. The SB can inhibit the growth of bacteria, fungi, and yeast. However, less is known of the effect of SB on host commensal microbial community compositions and their functions. In this study, we investigated the effect of SB on the growth and development of Drosophila melanogaster larvae and whether SB affects the commensal microbial compositions and functions. We also attempted to clarify the interaction between SB, commensal microbiota and host development by detecting the response of commensal microbiota after the intervention. The results show that SB significantly retarded the development of D. melanogaster larvae, shortened the life span, and changed the commensal microbial community. In addition, SB changed the transcription level of endocrine coding genes such as ERR and DmJHAMT. These results indicate that the slow down in D. melanogaster larvae developmental timing and shortened life span of adult flies caused by SB intake may result from the changes in endocrine hormone levels and commensal microbiota. This study provided experimental data that indicate SB could affect host growth and development of D. melanogaster through altering endocrine hormone levels and commensal microbial composition.

Dietary restriction and the transcription factor clock delay eye aging to extend lifespan in Drosophila Melanogaster

Many vital processes in the eye are under circadian regulation, and circadian dysfunction has emerged as a potential driver of eye aging. Dietary restriction is one of the most robust lifespan-extending therapies and amplifies circadian rhythms with age. Herein, we demonstrate that dietary restriction extends lifespan in Drosophila melanogaster by promoting circadian homeostatic processes that protect the visual system from age- and light-associated damage. Altering the positive limb core molecular clock transcription factor, CLOCK, or CLOCK-output genes, accelerates visual senescence, induces a systemic immune response, and shortens lifespan. Flies subjected to dietary restriction are protected from the lifespan-shortening effects of photoreceptor activation. Inversely, photoreceptor inactivation, achieved via mutating rhodopsin or housing flies in constant darkness, primarily extends the lifespan of flies reared on a high-nutrient diet. Our findings establish the eye as a diet-sensitive modulator of lifespan and indicates that vision is an antagonistically pleiotropic process that contributes to organismal aging.

Reduction of Drosophila Mitochondrial RNase P in Skeletal and Heart Muscle Causes Muscle Degeneration, Cardiomyopathy, and Heart Arrhythmia.

In this study, we examine the cause and progression of mitochondrial diseases linked to the loss of mtRNase P, a three-protein complex responsible for processing and cleaving mitochondrial transfer RNAs (tRNA) from their nascent transcripts. When mtRNase P function is missing, mature mitochondrial tRNA levels are decreased, resulting in mitochondrial dysfunction. mtRNase P is composed of Mitochondrial RNase P Protein (MRPP) 1, 2, and 3. MRPP1 and 2 have their own enzymatic activity separate from MRPP3, which is the endonuclease responsible for cleaving tRNA. Human mutations in all subunits cause mitochondrial disease. The loss of mitochondrial function can cause devastating, often multisystemic failures. When mitochondria do not provide enough energy and metabolites, the result can be skeletal muscle weakness, cardiomyopathy, and heart arrhythmias. These symptoms are complex and often difficult to interpret, making disease models useful for diagnosing disease onset and progression. Previously, we identified Drosophila orthologs of each mtRNase P subunit (Roswell/MRPP1, Scully/MRPP2, Mulder/MRPP3) and found that the loss of each subunit causes lethality and decreased mitochondrial tRNA processing in vivo. Here, we use Drosophila to model mtRNase P mitochondrial diseases by reducing the level of each subunit in skeletal and heart muscle using tissue-specific RNAi knockdown. We find that mtRNase P reduction in skeletal muscle decreases adult eclosion and causes reduced muscle mass and function. Adult flies exhibit significant age-progressive locomotor defects. Cardiac-specific mtRNase P knockdowns reduce fly lifespan for Roswell and Scully, but not Mulder. Using intravital imaging, we find that adult hearts have impaired contractility and exhibit substantial arrhythmia. This occurs for roswell and mulder knockdowns, but with little effect for scully. The phenotypes shown here are similar to those exhibited by patients with mitochondrial disease, including disease caused by mutations in MRPP1 and 2. These findings also suggest that skeletal and cardiac deficiencies induced by mtRNase P loss are differentially affected by the three subunits. These differences could have implications for disease progression in skeletal and heart muscle and shed light on how the enzyme complex functions in different tissues.

Sex-specific effects of PET-MPs on Drosophila lifespan.

In recent years, as an emerging pollutant, microplastic (MPs)pollution is gradually becoming a research hotspot. MPsare ubiquitous in the entire ecological environment. Organisms can be exposed to MPs via inhalation or ingestion. In view of the widespread of MPs pollution, the impact of MPs on biology should be further investigated. In previous experiments, we have conducted research on the physiology of Drosophila exposed to polyethylene terephthalatemicroplastics (PET-MPs). However, will the lifespan of Drosophila be affected under long-term PET-MPs exposure? The analysis of variance analysis of our experimental results indicates that there are significant differences between males and females, F(1, 895) = 68.19, p < 0.001, between PET-MPs concentration, F(3, 895) = 8.11, p < 0.001. There are also significant interactions between sex and MP concentration, F(3, 895) = 4.00, p < 0.01. For Cox and log-rank test, 1 g/L of PET-MPs prolongs the lifespan of male flies. The reason for this phenomenon may be the hormesis effect.

The effects of Cyperus rotundus L. extracts on the longevity of Drosophila melanogaster

Discovering plant extracts that can help delay the aging process is challenging as the world transitions into an aging society. Cyperus rotundus L. has long been used as a natural medication to cure a variety of disorders in the traditional medical systems of China, India, Africa, Japan, and Arab countries. C. rotundus may be a bioactive substance that can be used to prevent and treat various diseases, as well as prolong life and improve general well-being; however, no data supporting in vivo testing have been reported. This study investigates the effects of C. rotundus extract on the lifespan and stress-induced mortality in Drosophila melanogaster or fruit flies. Different solvent extractions, including ethanol (ECE), 70% ethanol (HECE), methanol (MCE), and water (WCE), of the rhizomes and tubers of C. rotundus were mixed into the diets of flies to determine the lifespan extension property. The most active extract was selected for further testing of resistance to oxidative stress, starvation, acetic acid, and survival from heavy metal-induced toxicity. The phytochemical profiles of the extract were analyzed using LC–MS. The results showed that the mean lifespan-prolonging effects of the extracts in flies were observed in the order of HECE>WEC>MCE>ECE. Supplementation with HECE at 10 mg/mL diet increased the antioxidant enzyme activities and decreased lipid peroxidation compared to the control group. After exposure to hydrogen peroxide and paraquat, Drosophila treated with HECE showed a significant increase in survival. Supplementation with HECE increased resistance to acetic acid and starvation. HECE supplementation also enhanced the survival of fruit flies from iron and aluminum toxicities. LC–MS analysis revealed the major components of epicatechin/catechin, p-coumaric acid, kaempferol, quercetin, and vanillin in HECE. These findings suggest that HECE promotes longevity and increases health by reducing oxidative damage, increasing the adaptive response in stress-induced aging, and decreasing heavy metal-induced toxicity.

Rapamycin Supplementation: Effect on Longevity in Drosophila melanogaster

Target of rapamycin (TOR) regulates a number of cellular responses, including autophagy. The purpose of this study was to investigate the effect on life span of supplementation with rapamycin dissolved in either dimethylsulfoxide (DMSO) or ethanol, in male and female flies of three strains of Drosophila melanogaster: Oregon R, w1118, and y w. The hypothesis was that longevity would be decreased regardless of strain, sex or solvent, consistent with an unpublished prior study using y w males in this laboratory, or alternatively that it would be increased as in publications from other laboratories. Flies were exposed to food supplemented with 200 µM rapamycin dissolved in one of the two solvents before being mixed into a standard agar‐yeast‐cornmeal‐sucrose medium. Supplementation was continuous beginning 2 d posteclosion. The mean life span of Oregon R females was diminished by rapamycin in both ethanol and DMSO solvents, by 17% and 13%, respectively (P &lt; 0.0005). Oregon R males also exhibited a shortened mean life span, which was significant in DMSO (8%, P = 0.008) but not ethanol (3%, P = 0.9). In contrast, w1118 female flies had a 4% increase in mean life span with rapamycin dissolved in ethanol (P &lt; 0.0005) but not DMSO (1% increase, P = 0.2). Rapamycin decreased life span in w1118 males, but the effect was significant only in DMSO (22%, P = 0.002), not ethanol (10%, P = 0.6). It decreased longevity significantly in y wflies of both sexes on both solvents, by 9% in females and 7‐12% in males (all P &lt; 0.0005 except male/DMSO P = 0.04). Notably, the life spans of control flies differed significantly between the solvents, being longer with ethanol for y w of both sexes and longer with DMSO for Oregon R males and w1118 males. In conclusion, these results show that effects of rapamycin on life span of Drosophila are sex‐, strain‐ and solvent‐dependent.

The tobacco phosphatidylethanolamine-binding protein NtFT4 increases the lifespan of Drosophila melanogaster by interacting with the proteostasis network.

Proteostasis reflects the well-balanced synthesis, trafficking and degradation of cellular proteins. This is a fundamental aspect of the dynamic cellular proteome, which integrates multiple signaling pathways, but it becomes increasingly error-prone during aging. Phosphatidylethanolamine-binding proteins (PEBPs) are highly conserved regulators of signaling networks and could therefore affect aging-related processes. To test this hypothesis, we expressed PEPBs in a heterologous context to determine their ectopic activity. We found that heterologous expression of the tobacco (Nicotiana tabacum) PEBP NtFT4 in Drosophila melanogaster significantly increased the lifespan of adult flies and reduced age-related locomotor decline. Similarly, overexpression of the Drosophila ortholog CG7054 increased longevity, whereas its suppression by RNA interference had the opposite effect. In tobacco, NtFT4 acts as a floral regulator by integrating environmental and intrinsic stimuli to promote the transition to reproductive growth. In Drosophila, NtFT4 engaged distinct targets related to proteostasis, such as HSP26. In older flies, it also prolonged Hsp26 gene expression, which promotes longevity by maintaining protein integrity. In NtFT4-transgenic flies, we identified deregulated genes encoding proteases that may contribute to proteome stability at equilibrium. Our results demonstrate that the expression of NtFT4 influences multiple aspects of the proteome maintenance system via both physical interactions and transcriptional regulation, potentially explaining the aging-related phenotypes we observed.