Effects Of Sterile Operation And Dietary Restriction On Lifespan And Metabolism In Mice

In recent years,with the continuous extension of human life expectancy and the increasingly serious problem of population aging,people pay more and more attention to diseases related to aging,followed by the research related to longevity and aging has made great progress.At present,researches have been made a series of progresses using some invertebrates such as caenorhabditis elegans and fruit flies as models.Aging has long been thought to be the result of cumulative damage to related molecules and cells,Dietary restrictions are considered the most effective way to extend life in many animals.In addition,researchers around the world pay more attention to the relationship between reproduction and aging recently.But there are so many questions about how exactly dietary restrictions extend life and what the molecular mechanism is.How does reproduction affect aging,and what are the major molecules or signaling pathways involved? this the mechanism is unclear yet.But the popular view is that dietary restriction can delay the aging process by reducing metabolic rate,reducing oxidative stress,improving insulin sensitivity,increasing autophagy,and delaying and inhibiting the occurrence of some age-related diseases.There are so many ways to prolong lifespan such as regulating TOR and AMP signaling,giving antioxidants and producing detoxification in experiments.In addition,it has reported that a negative correlation between fertility and longevity.Previous studies have found that reproductive signals can change fat metabolism,insulin signal,TOR signal and steroid signal pathway,which may extend life span through insulin-related pathway,lipid metabolism pathway,improvement of mitochondrial oxidation function and increase of autophagy function.So there’s an overlap between the molecular mechanisms of dieting and abstinence as ways to increase longevity.Based on the above reports,we established a mouse model of reproductive restriction and dietary restriction alone and combined,and conducted in vivo studieson the effects of various factors on metabolism in mice,which were mainly divided into following parts:Firstly,through the surgical removal of the gonads of male mice when they are young,we constructed sterile mouse models.We observed the influence of reproductive pathways on the life span and life state of mice on the mouse models,because the reproductive ability is impaired due to the lack of gonads.The sterile mouse model was constructed for two reasons,one of which was to verify the effect of reproductive signals on longevity in mammals.On the other hand,a mammalian model was constructed to compare the difference of substance metabolism pathways between sterile and fertile mouse models.So we can explore the respective mechanisms of castration and restricted diet in delaying senility and the possible overlapping mechanisms of their mutual influences.There was no significant difference in motor ability and cognitive ability between castrated mice and non-castrated mice,and there are no other signs of dysplasia other than the reproductive system.Secondly,the expression of the longevity related gene FOXO3 in our dietary restriction,sterile and crossover models was tested at the molecular and individual levels to see if it was consistent with the results reported in the literature in other species.Our results suggest that sterile alone,dietary restriction with or without sterile can promote FOXO3 expression.Finally,we investigated the effects of sterile and dietary restriction on the expression of certain key functional proteins in animal metabolic pathways.Our research focuses on the regulation of lipid metabolism related enzymes and the expression of elongase of very long chain fatty acids,we found that the expression of PPARα,a key transcription factor regulating lipid metabolism,was significantly up-regulated after sterile operation though qPCR.It suggested that lipid metabolism was active in sterile animals.The expression of fatty acid elongase and the expressionof related ELOVL family genes were analyzed,and we especially compared the expression of elongase of very long chain fatty acid 3(ELOVL3)in sterile mice with caenorhabditis elegans.The results showed that sterile operation significantly promoted the high expression of ELOVL3,which may be related to the de inhibition of NR1D1.Conclusion: sterile operation and dietary restriction have certain promoting effects on delaying senility and prolonging life span of mice,and the main mechanism may be related to the change of fat metabolism pathway.