Sexual Dimorphism In The Nutritional Requirement For Lifespan And Feeding Preference In Drosophila

Aging is a process in which the normal physiological function of an organism declines with age.The influencing factors for aging include both genetic and environmental factors,of which nutrition is one of the important environmental factors.Drosophila is a classic model animal for aging biology and nutritional physiology.Based on conserved nutrientsensing pathways from invertebrate to mammals,using Drosophila to study the mechanism of nutrient regulation of aging will be able to provide new insights into aging and anti-aging research in humans.Previous studies have clarified the nutritional requirements of Drosophila at the developmental stage,but it’s still unclear about the basic nutritional requirements of adult flies to maintain full length of life,and whether there are gender differences in the nutritional components required for longevity.In addition,the relationship between the nutritional requirements of Drosophila longevity and feeding behavior also needs to be revealed.The study of these questions will promote our understanding of the mechanisms by which nutrition regulates aging and behavior,gain more insight into the causes of sex differences in lifespan,and define the scope of application of Drosophila as a model animal for nutrition and aging research.We have investigated the basic nutritional requirements of adult flies for maintaining normal lifespan and their effects on feeding behavior using a chemically defined medium.The main results are as follows:1.Male flies generally required significantly lower levels of various nutrients to maintain normal lifespan than females.The sex difference in nutritional requirements for lifespan maintenance between male and female flies is mainly manifested in the difference in cholesterol and B-group vitamins requirements.From 48 hours after eclosion,chronic deficiency of cholesterol and vitamins in adult stage has no effect on male lifespan,but greatly shortens female lifespan by ~ 50%.In addition,male and female flies also show sex differences in requirements for sugar and amino acids for lifespan,the minimum sucrose and amino acid levels required by male flies to maintain normal lifespan are only 10% ~ 20% of the those required by females.2.Sex differences in the nutritional requirements of Drosophila for maintaining normal lifespan are independent of the Y chromosome.In the absence of cholesterol or vitamins,the lifespan phenotype of XO males was consistent with that of wild-type XY males;The lifespan phenotype of XXY females was consistent with that of wild-type XX females.3.Female oogenesis is the key cause of this gender difference in life-sustaining nutritional requirements.The ovoD1 sterile mutant significantly rescue female lifespan under sucrose,amino acid,cholesterol,and vitamin deficiencies.4.Mutations in the insulin signaling pathway significantly extend the lifespan of females under cholesterol-deficient conditions.Insulin receptor mutation In RE19 and insulin receptor substrate mutation chico1 had no effect on the lifespan of female flies under amino acid and vitamin deficiency conditions,but significantly increased the survival of females under cholesterol deficiency conditions.Given that the phosphorylation level of Akt was not significantly reduced in sterile mutant ovoD1 females relative to wildtype females,it suggests that the survival advantage of ovoD1 females under cholesteroldeficient conditions is not dependent on the insulin signaling pathway.5.There are significant sex differences in the feeding preferences of flies for nutrients.Using 32 P radiolabeled feeding assay,we revealed that wild-type females had a significantly higher preference for protein than males and infertile ovoD1 females;Flies also showed a significant feeding preference for diets containing vitamins,but the preference for vitamins in females was significantly higher than it in males.Among the seven B vitamins that flies cannot synthesize in vivo,females show a strong feeding preference for folic acid and riboflavin,while males only have a slight preference for folic acid.The taste sensitivity of females to folic acid and riboflavin was four orders of magnitude higher than their sensitivity to sucrose.6.The vitamin preference in Drosophila require both external taste bristles and pharyngeal taste organs.Poxn70/?M22 mutants,which lack functional external taste bristles,showed no preference for riboflavin but maintained preference for folic acid.Further overexpression of Kir-2.1 in taste neurons to silence pharyngeal taste receptors on the basis of Poxn70/?M22 mutants abolished female feeding preferences for both folic acid and riboflavin simultaneously.Thus,taste perception and feeding preference for riboflavin in female flies require functional external taste bristles,whereas taste perception and feeding preference for folic acid require pharyngeal taste receptors.In this study,we revealed the sexual dimorphism in the nutritional requirement for adult lifespan in Drosophila.We uncovered that the nutritional requirement of male flies was generally lower than that of females,with the difference in cholesterol and vitamin requirements between sexes being the most prominent.Female oogenesis rather than chromosomal karyotype and mating status was the key cause of this gender difference in life-sustaining nutritional requirements.Our studies also demonstrated that dietary micronutrients could impact consummatory feeding behavior and highlight a possible sensoriperceptual link between vitamin-directed behavior and nutritional need.This study provides important basic data for aging research in the context of nutritional physiology,increases our understanding of the mechanisms of sex difference in lifespan and the mode of action of dietary nutrition with animal behavior.