Dietary choices are influenced by genotype, mating status, and sex in <i>Drosophila melanogaster</i>

Camus, M. Florencia; Huang, Chun-Cheng; Reuter, Max; Fowler, Kevin

doi:10.1002/ece3.4055

Cited by 41 publications

(57 citation statements)

References 35 publications

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“…One observation we made is that the effects of Zol varied depending on time of administration, dose and sex differences that may be partly due to alternate drug uptake by males and females. In females, egg production requires higher levels of nutritional input than required by males, resulting in increased food consumption and, presumably, increased drug uptake (Camus, Huang, Reuter, & Fowler, 2018). By contrast, in the FPPS mutants, where the action of the enzyme is disrupted independently of drug uptake, similar lifespan extension is observed suggesting that the effect of mevalonate pathway inhibition on lifespan is unlikely to be sexually dimorphic.…”

Section: Discussionmentioning

confidence: 99%

Zoledronate extends healthspan and survival via the mevalonate pathway in a FOXO-dependent manner

Chen

Cordero

Slack

et al. 2020

Preprint

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Increased longevity has not been paralleled by extended healthspan, resulting in more years spent with multiple diseases in older age. As such, interventions to improve healthspan are urgently required. Zoledronate is a nitrogen containing bisphosphonate, which inhibits the farnesyl pyrophosphate synthase (FPPS) enzyme, central to the mevalonate pathway. It is already used clinically to prevent fractures in osteoporotic patients, who have been reported to derive unexpected and unexplained survival benefits. In this study we show that zoledronate has beneficial effects on both lifespan and healthspan using Drosophila as a model. We found that zoledronate extended lifespan, improved climbing activity and reduced intestinal epithelial dysplasia and permeability in aged flies. Mechanistic studies showed that zoledronate conferred resistance to oxidative stress and reduced accumulation of X-rayinduced DNA damage via inhibition of FPPS. Moreover, zoledronate inhibited pAKT in the mTOR pathway and functioned via dFOXO, a molecule associated with increased longevity, downstream of the mevalonate pathway. Taken together, our work indicates that zoledronate, a drug already widely used and dosed only once a year to prevent osteoporosis, modulates important mechanisms of ageing. Its repurposing holds great promise as a treatment to improve healthspan.

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Section: Discussionmentioning

confidence: 99%

Zoledronate extends healthspan and survival via the mevalonate pathway in a FOXO-dependent manner

Chen

Cordero

Slack

et al. 2020

Preprint

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“…We note, however, that the transcriptional profiles in that study were measured in the heads of virgin flies. Data on nutritional preference suggests that male and female dietary requirements, and hence presumably also their physiological states, are more similar in virgins than mated flies [11], which might also contribute to the concordant responses. Because we use mated flies for the experiments reported here, this caveat does not apply to the current study.…”

Section: A Shared Metabolic Core Transcriptomementioning

confidence: 99%

“…These choices are further adapted to reflect the individual's current condition and reproductive investment [9,10]. For example, Camus et al [11] found that the female preference for protein in fruit flies was significantly higher in mated females (who require resources to produce eggs) than virgins, while the preferences of males (who start producing sperm before reaching sexual maturity) did not significantly differ between mated and virgin flies.…”

Section: Introductionmentioning

confidence: 99%

Sex-specific transcriptomic responses to changes in the nutritional environment

Camus

Piper

Reuter

2019

Preprint

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23Males and females typically pursue divergent reproductive strategies and accordingly require 24 different dietary compositions to maximise their fitness. Here we move from identifying sex-25 specific optimal diets to understanding the molecular mechanisms that underlie male and 26 female responses to dietary variation. We examine male and female gene expression on male-27 optimal (carbohydrate-rich) and female-optimal (protein-rich) diets. We find that the sexes 28 share a large core of metabolic genes that are concordantly regulated in response to dietary 29 composition. However, we also observe smaller sets of genes with divergent and opposing 30 regulation, most notably in reproductive genes which are over-expressed on each sex's 31 optimal diet. Our results suggest that nutrient sensing output emanating from a shared 32 metabolic machinery are reversed in males and females, leading to opposing diet-dependent 33 regulation of reproduction in males and females. Further analysis and experiments suggest 34 that this reverse regulation occurs within the IIS/TOR network. 35 36 [3]. 46Studies in insect species [3][4][5][6][7] have shown that the two sexes require different diets to 47 maximise fitness. Female fitness is typically maximised on a high concentration of protein, 48 which fulfils the demands of producing and provisioning eggs. Males, in contrast, achieve 49 optimal fitness with a diet consisting of more carbohydrate, which can fuel activities such as 50 locating and attracting mates. Work on nutritional choices has shown that individuals tailor 51 their diet in line with their physiological needs. In insects, females overall prefer diets with 52 higher protein content, whereas males chose a more carbohydrate-rich diet [8, 9]. These 53 choices are further adapted to reflect the individual's current condition and reproductive 54 investment [9, 10]. For example, Camus et al. [11] found that the female preference for 55 protein in fruit flies was significantly higher in mated females (who require resources to 56 produce eggs) than virgins, while the preferences of males (who start producing sperm before 57 reaching sexual maturity) did not significantly differ between mated and virgin flies. 58But individuals not only choose diets to suit their needs where possible, they also adapt 59 their physiology and reproductive investment in response to the quality and quantity of 60 nutrition available. This has been studied extensively using experiments that either alter the 61 macronutrients composition (carbohydrates vs. protein) of the diet while keeping the overall 62 caloric intent constant, or by manipulating the overall nutrient content of the food-dietary 63 restriction (DR). These studies have shown that a wide range of life history traits respond to 64 changes in both the composition of the food [7, 12, 13] and the quantity of nutrients supplied 65 [14][15][16]. For example, DR typically causes an extension of lifespan at the cost of reduced 66reproduction [17], and a similar response can be triggered ...

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“…Drosophila melanogaster has been used as a model for nutritional physiology studies for many years (Piper, 2017;Rauser, Mueller, & Rose, 2004;Tatar, Post, & Yu, 2014), and their requirements for development and female reproduction are well studied (Begg & Robertson, 1950;Consuegra et al, 2019;Piper, 2017;Sang & King, 1961). We also know that the lifespan of male and female adults respond differently to dietary interventions and that the sexes show different preference in macronutrient balance (Bowman & Tatar, 2016;Camus, Huang, Reuter, & Fowler, 2018;Chandegra, Tang, Chi, & Alic, 2017;Lee, Kim, & Min, 2013;Magwere, Chapman, & Partridge, 2004;Regan et al, 2016;Wu et al, 2020), but no one has systematically determined the minimal requirements of each nutrient class for adult lifespan and whether these requirements differ between the sexes. Defining these limits is important since it is fundamental to understanding how adult-specific diet interventions, such as DR and DB, may be operating to modify lifespan.…”

Section: Introductionmentioning

confidence: 99%

Sexual dimorphism in the nutritional requirement for adult lifespan in Drosophila melanogaster

Cheng

et al. 2020

Aging Cell

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The nutritional requirements of Drosophila have mostly been studied for development and reproduction, but the minimal requirements for adult male and female flies for lifespan have not been established. Following development on a complete diet, we find substantial sex difference in the basic nutritional requirement of adult flies for full length of life. Relative to females, males require less of each nutrient, and for some nutrients that are essential for development, adult males have no requirement at all for lifespan. The most extreme (and surprising) sex differences were that chronic cholesterol and vitamin deficiencies had no effect on the lifespan of adult males, but they greatly decreased lifespan in females. Female oogenesis rather than chromosomal karyotype and mating status is the key cause of this gender difference in life‐sustaining nutritional requirements. These data are important to the way we understand the mechanisms by which diet modifies lifespan.

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Dietary choices are influenced by genotype, mating status, and sex in Drosophila melanogaster

Cited by 41 publications

References 35 publications

Zoledronate extends healthspan and survival via the mevalonate pathway in a FOXO-dependent manner

Zoledronate extends healthspan and survival via the mevalonate pathway in a FOXO-dependent manner

Sex-specific transcriptomic responses to changes in the nutritional environment

Sexual dimorphism in the nutritional requirement for adult lifespan in Drosophila melanogaster

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