Sex Differences In Food Intake With Age And The Mechanism Of Cholesterol Competition Shortening Lifespan Induced By Oviposition In Drosophila

Feeding is the most fundamental behavior of animals,which determines when,what and how much for them to eat.Moreover,feeding is a complex process,which is regulated by physiological states and various nerves.However,there is still a lack of understanding of the changes of animal feeding behavior,including food intake,with age,and the interconnection between feeding and longevity.How does feeding behavior change at different time points of aging? How does feeding behavior interact with aging? Can aging be interfered with by intervening age-related changes in feeding behavior? These are all questions worth exploring.Different physiological stages of the organism need different ratio of nutrients.There is difference for the nutritional requirements between reproduction and maintenance of the organism.Studies in the nematode,flies,companion dogs and mice show that under certain conditions,there is a negative correlation between fecundity and longevity.Previous studies suggested that an important reason for the negative correlation was the nutritional competition.However,due to the complexity of dietary nutritional composition,the contribution and primary and secondary connection of various nutrients in regulating longevity in reproductive nutrition competition are not clear.The mechanism by which oviposition competition affects lifespan through other tissues and organs is not fully understood.In order to study the change of animal feeding behavior,the relationship between lifespan and reproductive capacity,we took Drosophila as model organism to study the changes of food intake with time and the main nutrients that limit reproduction(oviposition)and lifespan,laying a foundation for the study of nutrition and aging.The main research results are as follows:1.We designed a method to detect the food intake of flies by collecting excreta.Compared with the previous method,this method has the advantage of detecting the food intake in more accurate time points and for a long range.2.The overall food intake of Drosophila decreased with aging,but the change pattern of early food intake had gender difference.We found that the main reason for the difference of early changes of food intake is due to the change of female oviposition.3.Cholesterol is the key nutrient for fly’s longevity mediated by fecundity.In the absence of amino acids,vitamins,or sugar respectively,flies minimize the oviposition rapidly to meet the needs of somatic cell maintenance,while in the absence of cholesterol,eggs producing by Drosophila decreases very little,resulting in a huge compensation from lifespan.We confirmed that the cholesterol competition caused by oviposition significantly negatively correlation between lifespan and reproductive ability.4.The cholesterol competition of reproductive capacity for cholesterol results in a shorter lifespan of flies,mainly through the destruction of fly intestinal barrier.Severe destruction of the intestinal barrier is the most typical phenotype of cholesterol deficiency.5.Cholesterol metabolism disorder and cholesterol deficiency have the same phenotype,such as lifespan shortening and intestinal barrier damadged.Regulating reproduction can also save the shortened lifespan under cholesterol metabolism disorder.6.The ability to inhibit IIS and m TOR signaling partially rescues shortened lifespan in cholesterol deficiency conditions,mainly by reducing egg production.In this study,using Drosophila as a model organism and a new detection method for fly food intake,we found that there was a gender difference in the change of Drosophila food intake in the early stage.In female,the main reason for the change of decrease in food intake is due to reduced nutritional requirements as egg production decreases.We further discovered that changes in dietary cholesterol levels had a smaller effect on the eggs laid of Drosophila than that from other nutrients.In cholesterol-restricted conditions,Drosophila lacks a feedback regulatory mechanism by that it should reduce cholesterol consumption for reduces egg laying.It is this lack of sensitivity to low cholesterol levels and feedback mechanisms that lead to age-related loss of intestinal barrier integrity and disruption of homeostasis,fat metabolism disorders,and shortened lifespan.The results of this study provide research experimental data for exploring the nutritional composition of optimal longevity diet under different physiological conditions,and also provide reference for human nutritional health.