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Comparison of mean longevities between previously published longevities in [26] (a) and [28] (b) with the current experiment. Data in (a) are from virgin males (blue) and females (red), while data in (b) are from mated females. Black line is the line of symmetry.
Source publication
Costs of reproduction are seemingly ubiquitous across the animal kingdom, and these reproductive costs are generally defined by increased reproduction leading to decreases in other fitness components, often longevity. However, some recent reports question whether reproductive costs exist in every species or population. To provide insight on this is...
Citations
... Reproduction has a huge energy burden on lower model organisms. Studies have shown that interventions which reduced fecundity in ies also improved their lifespan by conserving and channeling energy earmarked for reproductive output (De Loof, 2011;Hoffman et al., 2021). E cacy of α-lipoic acid observed in our study plausibly depended on rearing conditions as well as gender of ies fed with HFD. ...
Consumption of a high fat diet is accompanied with the risk of obesity and early onset of age-associated complications. Hence, dietary interventions are imperative to combat this. α-lipoic acid has been shown to hinder diet-induced obesity in model organisms. Recent studies hint at probable lifespan extending efficacy of α-lipoic acid as well. Drosophila melanogaster has emerged as a robust model organism for longevity studies. In this study, α-lipoic acid was investigated for its efficacy to improve lifespan and age-associated physiology in Canton-S strain of Drosophila melanogaster fed with a high fat diet. Furthermore, as mating status has a significant impact on survival in fruit-flies, flies were reared in two experimental groups – group one in which males and females were reared together and group two in which males and females were reared separately. In group one, α-lipoic acid improved mean lifespan, reduced fecundity of females and reduced mean body weight of flies at dose range of 2mM – 2.5mM, respectively. In group two, α-lipoic acid improved mean lifespan, reduced fecundity of females and reduced mean body weight of flies at dose range of 1mM – 2.5mM, respectively. Improved climbing efficiency was observed with α-lipoic acid at dose range of 1.5mM – 2.5mM in flies of group one and 1mM – 2.5mM in flies of group two, respectively. Administration of α-lipoic acid improved resistance to oxidative stress in only female flies of group one at 2.5mM whereas in group two, both male and female flies exhibited improved resistance to oxidative stress with α-lipoic acid at dose range of 2mM – 2.5mM, respectively. Male and female flies of only group one showed improved resistance to heat shock stress with α-lipoic acid at dose range of 2mM – 2.5mM. Only female flies of group two exhibited a small significant improvement in recovery time following cold shock with α-lipoic acid only at 2.5mM. No significant change in resistance to starvation stress was observed with any dose of α-lipoic acid in either group of flies. To summarize, data from this study suggested a probable dose and gender dependent efficacy of α-lipoic acid in flies fed with a high fat diet; this efficacy was also significantly impacted by mating status of flies due to varied rearing conditions.
... In organisms with separate sexes male and female lifespans are often characteristically different. SDL can vary in direction and magnitude across species [1][2][3][4] and can also show plasticity within species in response to variation in diet and reproductive activity [5][6][7][8][9][10][11][12]. However, much about the determination of sex-specific lifespan remains unclear [3,13]. ...
... One is the sensitivity of female lifespan in particular to mating status [45,48,64,67]. For example, single matings at the start of life have minimal effects on female lifespan [4,46], yet intermittent or continual exposure to males can shorten it dramatically [45,48]. ...
Males and females rarely express the same length of life. Here we studied how socio-sexual exposure shapes male and female age-specific mortality rates in Drosophila melanogaster. We maintained focal females and males within large, replicated cohorts throughout life with individuals of the same or opposite sex. Consistent with previous works, we found that females kept throughout their lives with males had only half the lifespan of those maintained throughout life at the same density in same-sex cohorts. In contrast, only a small lifespan decrease was observed in the corresponding male treatments and the reduction in male lifespan following exposure throughout life to other males or to females was similar. Deconvolution of underlying ageing parameters revealed that changes in lifespan were underpinned by opposing effects on actuarial ageing in males versus females. Exposure to the opposite or same sex increased initial mortality rate in both sexes. However, in females, increasing exposure to males increased the rate-of-ageing, while increasing exposure to females actually decreased it. The effects were in the opposite direction in males and were much smaller in magnitude. Overall, the findings were consistent with reports suggesting that exposure to the same versus opposite sex can affect survival differently in males and females. However, they also reveal a new insight - that overall lifespan can be underpinned by key differences in actuarial senescence in each sex. The findings suggest that responses to same or opposite sex exposure may have fundamentally and qualitatively different physiological consequences for health in males and females.
... Several laboratory studies have revealed a significant 'cost of mating' to Drosophila females in the form of reduced longevity [72][73][74][75]. However, other studies have previously reported contrary results in both wild-caught [75] and laboratory-reared [76] flies. As we have observed in our study, they also showed no cost of mating in mated females flies compared to virgins when uninfected. ...
... These discrepancies are mostly driven by both the genetic background and the environment. Aspects as dietary and/or seasonal husbandry, even within the same laboratory, can substantially affect the study of mating costs and sex differences [75,76]. However, in our study all experiments were performed independently and per triplicate. ...
Sex and reproductive status of the host have a major impact on the immune response against infection. Our aim was to understand their impact on host tolerance or resistance in the systemic Mycobacterium marinum infection of Drosophila melanogaster. We measured host survival and bacillary load at time of death, as well as expression by quantitative real-time polymerase chain reaction of immune genes (diptericin and drosomycin). We also assessed the impact of metabolic and hormonal regulation in the protection against infection by measuring expression of upd3, impl2 and ecR. Our data showed increased resistance in actively mating flies and in mated females, while reducing their tolerance to infection. Data suggests that Toll and immune deficiency (Imd) pathways determine tolerance and resistance, respectively, while higher basal levels of ecR favours the stimulation of the Imd pathway. A dual role has been found for upd3 expression, linked to increased/decreased mycobacterial load at the beginning and later in infection, respectively. Finally, impl2 expression has been related to increased resistance in non-actively mating males. These results allow further assessment on the differences between sexes and highlights the role of the reproductive status in D. melanogaster to face infections, demonstrating their importance to determine resistance and tolerance against M. marinum infection.
... However, even focusing on nonvirgin flies, the direction of lifespan differences between male and female flies has not always been consistent in previous studies. While it is generally believed that female flies live longer than males [17][18][19][20], many reports have shown inconclusive results [21][22][23]. Surveys based on multiple strains even suggested longer male lifespans [12,24]. The sex differences in fly lifespan, therefore, is still controversial. ...
Animals exhibit different extents of sexual dimorphism in a variety of phenotypes. Sex differences in longevity, one of the most complex life history traits, have also been reported. Although lifespan regulation has been studied extensively in the fruit fly, Drosophila melanogaster, the sex differences in lifespan have not been consistent in previous studies. To explore this issue, we revisited this question by examining the lifespan and stress resistance of both sexes among 15 inbred strains. We first found positive correlations between males and females from the same strain in terms of lifespan and resistance to starvation and desiccation stress. Although the lifespan difference between male and female flies varied greatly depending on the strain, males across all strains collectively had a longer lifespan. In contrast, females showed better resistance to starvation and desiccation stress. We also observed greater variation in lifespan and resistance to starvation and desiccation stress in females. Unexpectedly, there was no notable correlation observed between lifespan and the three types of stress resistance in either males or females. Overall, our study provides new data regarding sexual dimorphism in fly lifespan and stress resistance; this information may promote the investigation of mechanisms underlying longevity in future research.
... However, observed lifespan in our study is shorter than in previous studies using the same Oregon R strain (Ganetzky and Flanagan, 1978;Malacrida et al., 2022), which may have influenced the observed exposure effects. Differing lifespans between sexes can depend on treatment stress, mating status, and their genotypes (Hoffman et al., 2021). Due to a lack of a sex-specific effect in our study, we correlated the expression of DEGs and lifespan across exposure doses with the two sexes combined. ...
Background:
Legacy per- and polyfluoroalkyl substances (PFAS), known for their environmental persistence and bio-accumulative properties, have been phased out in the U.S. due to public health concerns. A newer polymerization aid used in the manufacture of some fluoropolymers, hexafluoropropylene oxide-dimer acid (HFPO-DA), has lower reported bioaccumulation and toxicity, but is a potential neurotoxicant implicated in dopaminergic neurodegeneration.
Objective:
We investigated HFPO-DA's bio-accumulative potential and sex-specific effects on lifespan, locomotion, and brain gene expression in fruit flies.
Methods:
We quantified bioaccumulation of HFPO-DA in fruit flies exposed to 8.7×104µg/L of HFPO-DA in the fly media for 14 days via UHPLC-MS. Long-term effect on lifespan was determined by exposing both sexes to 8.7×102 - 8.7×105µg/L of HFPO-DA in media. Locomotion was measured following 3, 7, and 14 days of exposures at 8.7×101 - 8.7×105µg/L of HFPO-DA in media, and high-throughput 3'-end RNA-sequencing was used to quantify gene expression in fly brains across the same time points.
Results:
Bioaccumulation of HFPO-DA in fruit flies was not detected. HFPO-DA-induced effects on lifespan, locomotion, and brain gene expression, and lowest adverse effect level (LOAEL) showed sexually dimorphic patterns. Locomotion scores significantly decreased in at least one dose at all time points for females and only at 3-day exposure for males, while brain gene expression exhibited non-monotonic dose-response. Differentially expressed genes correlated to locomotion scores revealed sex-specific numbers of positively and negatively correlated genes per functional category.
Conclusion:
Although HFPO-DA effects on locomotion and survival were significant at doses higher than the US EPA reference dose, the brain transcriptomic profiling reveals sex-specific changes and neurological molecular targets; gene enrichments highlight disproportionately affected categories, including immune response: female-specific co-upregulation suggests potential neuroinflammation. Consistent sex-specific exposure effects necessitate blocking for sex in experimental design during HFPO-DA risk assessment.
... In Drosophila suzukii (the Spotted Wing Drosophila or SWD), it has been shown that exposure to higher yeast leads to more mated female flies, but it did not lead to an increase in oviposition [55]. While a link between mating frequency and a decrease in lifespan has been proposed [56], it is still heavily debated in the Drosophila literature [57]. Further experiments focused either on female or male longevity should control for mating activity on different yeast quantities. ...
Nutrition and growth are strongly linked, but not much is known about how nutrition leads to growth. To understand the connection between nutrition through the diet, growth, and proliferation, we need to study the phenotypes resulting from the activation and inhibition of central metabolic pathways. One of the most highly conserved metabolic pathways across eukaryotes is the Target of Rapamycin (TOR) pathway, whose primary role is to detect the availability of nutrients and to either induce or halt cellular growth. Here we used the model organism Drosophila melanogaster (D. mel.) and three non-model Drosophila species with different dietary needs, Drosophila guttifera (D. gut.), Drosophila deflecta (D. def.), and Drosophila tripunctata (D. tri.), to study the effects of dietary amino acid availability on fecundity and longevity. In addition, we inhibited the Target of Rapamycin (TOR) pathway, using rapamycin, to test how the inhibition interplays with the nutritional stimuli in these four fruit fly species. We hypothesized that the inhibition of the TOR pathway would reverse the phenotypes observed under conditions of overfeeding. Our results show that female fecundity increased with higher yeast availability in all four species but decreased in response to TOR inhibition. The longevity data were more varied: most species experienced an increase in median lifespan in both genders with an increase in yeast availability, while the lifespan of D. mel. females decreased. When exposed to the TOR inhibitor rapamycin, the life spans of most species decreased, except for D. tri, while we observed a major reduction in fecundity across all species. The obtained data can benefit future studies on the evolution of metabolism by showing the potential of using non-model species to track changes in metabolism. Particularly, our data show the possibility to use relatively closely related Drosophila species to gain insight on the evolution of TOR signaling.
... In Drosophila melanogaster, male lifespan is reduced by mating and by even just the perception of the opposite sex (Gendron et al., 2014). Likewise, females living in the presence of males have shorter lifespan than expected when accounting for egg production (Harvanek et al., 2017;Landis et al., 2021;Partridge & Farquhar, 1981;Partridge et al., 1987), but a recent study found surprisingly small effects of mating on lifespan across 15 Drosophila strains (Hoffman et al., 2021). In many species, parental care is strongly dimorphic (reviewed in Clutton-Brock & Scott, 1991). ...
Sex differences in aging occur in many animal species, and they include sex differences in lifespan, in the onset and progression of age‐associated decline, and in physiological and molecular markers of aging. Sex differences in aging vary greatly across the animal kingdom. For example, there are species with longer‐lived females, species where males live longer, and species lacking sex differences in lifespan. The underlying causes of sex differences in aging remain mostly unknown. Currently, we do not understand the molecular drivers of sex differences in aging, or whether they are related to the accepted hallmarks or pillars of aging or linked to other well‐characterized processes. In particular, understanding the role of sex‐determination mechanisms and sex differences in aging is relatively understudied. Here, we take a comparative, interdisciplinary approach to explore various hypotheses about how sex differences in aging arise. We discuss genomic, morphological, and environmental differences between the sexes and how these relate to sex differences in aging. Finally, we present some suggestions for future research in this area and provide recommendations for promising experimental designs. Sex difference in aging occurs across the animal kingdom, but there is considerable variation and they are not universal. The processes leading to sex‐specific aging are poorly understood and might originate in sex‐specific genome architecture, organismal biology, or environmental interactions. Here, we take a comparative approach to review the various hypotheses and suggest promising areas of research for further study.
Lifespan is a complex quantitative trait involving genetic and non-genetic factors as well as the peculiarities of ontogenesis. As with all quantitative traits, lifespan shows considerable variation within populations and between individuals. Drosophila, a favourite object of geneticists, has greatly advanced our understanding of how different forms of variability affect lifespan. This review considers the role of heritable genetic variability, phenotypic plasticity and stochastic variability in controlling lifespan in Drosophila melanogaster. We discuss the major historical milestones in the development of the genetic approach to study lifespan, the breeding of long-lived lines, advances in lifespan QTL mapping, the environmental factors that have the greatest influence on lifespan in laboratory maintained flies, and the mechanisms, by which individual development affects longevity. The interplay between approaches to study ageing and lifespan limitation will also be discussed. Particular attention will be paid to the interaction of different types of variability in the control of lifespan.
Genome-wide association studies have advanced our understanding of complex traits, but studying how a GWAS variant can affect a specific trait in the human population remains challenging due to environmental variability. Drosophila melanogaster is in this regard an excellent model organism for studying the relationship between genetic and phenotypic variation due to its simple handling, standardized growth conditions, low cost, and short lifespan. The Drosophila Genetic Reference Panel (DGRP) in particular has been a valuable tool for studying complex traits, but proper harmonization and indexing of DGRP phenotyping data is necessary to fully capitalize on this resource. To address this, we created a web tool called DGRPool (dgrpool.epfl.ch), which aggregates phenotyping data of 935 phenotypes across 125 DGRP studies in a common environment. DGRPool enables users to download data and run various tools such as genome-wide association analyses (GWAS) and Phenome-WAS analyses. As a proof-of-concept, DGRPool was used to study the longevity phenotype and uncovered both established and unexpected correlations with other phenotypes such as locomotor activity, sleep duration, and oxidative stress resistance. DGRPool has the potential to facilitate new genetic and molecular insights of complex traits in Drosophila and serve as a valuable, interactive tool for the scientific community.
Investigators traditionally use randomized designs and corresponding analysis procedures to make causal inferences about the effects of interventions, assuming independence between an individual’s outcome and treatment assignment and the outcomes of other individuals in the study. Often, such independence may not hold. We provide examples of interdependency in model organism studies and human trials and group effects in aging research and then discuss methodologic issues and solutions. We group methodologic issues as they pertain to (1) single-stage individually randomized trials; (2) cluster-randomized controlled trials; (3) pseudo-cluster-randomized trials; (4) individually randomized group treatment; and (5) two-stage randomized designs. Although we present possible strategies for design and analysis to improve the rigor, accuracy and reproducibility of the science, we also acknowledge real-world constraints. Consequences of nonadherence, differential attrition or missing data, unintended exposure to multiple treatments and other practical realities can be reduced with careful planning, proper study designs and best practices. In this Perspective, the authors discuss experimental scenarios that breach the assumption of independence of all samples or participants in a study, specifically in aging research. They outline various strategies to improve the rigor and accuracy of the science with design and analysis solutions, while also considering real-world constraints.
