Study On The Mechanism Of Lacticaseibacillus Rhamnosus Probio-M9 On Lifespan Of Caenorhabditis Elegans

Aging is a time-dependent biologically complex process,which is a degenerative change of the body with the increase of age,mainly affected by factors such as genetics,environment and dietary habits.Probiotics have such probiotic properties as maintaining the balance of intestinal flora,improving body immunity,reducing related inflammation and lowering cholesterol content,but there are few reports on probiotics helping to delay host aging.In this study,the model organism Caenorhabditis elegans was used to investigate the effects of Lacticaseibacillus rhamnosus Probio-M9 from breast milk on the life cycle,developmental capacity,body size,body swing speed,pharyngeal pumping rate,locomotory ability and lipofuscin accumulation level of nematodes,based on the p38MAPK signaling pathways,nutrient-sensing signaling pathways,and mitochondrial unfolded protein response(UPR^mt),combined with the differentially expressed metabolites of Probio-M9,analyzed the possible mechanisms of Probio-M9 to extend the lifespan of nematodes,and revealed the molecular mechanism of Probio-M9 to delay host aging.The main results are as follows:(1)Without affecting the life and development cycle of nematodes,feeding Probio-M9 can improve the body swing speed,the pharyngeal pumping rate and the locomotory ability in the elderly nematodes,and reduce the accumulation levels of lipofuscin in the elderly nematodes and enhance heat resistance of nematodes,extend the lifespan of nematodes by 30%.(2)Probio-M9 in the state of live bacteria attaches to nematodes'intestines and promotes their health by activating the host's defense mechanism.Heat-inactivated Probio-M9 unable to extend the lifespan of nematodes.(3)OP50+Probio-M9 unable to extend the p38 cascade,daf-2(e1370)and DAF-2downstream transcription factor skn-1(mg570)loss-of-function mutants lifespan.Therefore,Probio-M9 enhances the defensive ability of nematodes by activating the p38cascade and daf-2 signaling pathways,thereby delaying host aging.(4)OP50+Probio-M9 enhances the expression of the nematodes UPR^mt reporter gene hsp-6p::gfp intestinal and tail fluorescence,and unable to extend the loss-of-function mutants lifespan of transcription factor atfs-1(gk3034),and the electron transport chain(ETC)controlling the mitochondrial-nucleus balance comprises genes isp-1(qm150)and nuo-6(qm200).Therefore,Probio-M9 protects and repairs damaged mitochondria can maintain metabolic stability,thereby extending lifespan of nematodes.(5)The results of bacterial metabolomics sequencing showed that amino acids,sphingolipids,phenolic acids,as well as indole and substituted derivatives were significantly regulated differentially expressed,which may be the key metabolites of Probio-M9 to extend lifespan of nematodes.This study provides a theoretical basis for further exploring Probio-M9 as a potential dietary supplement to delay host aging,and also provides new methods and ideas for further analyzing probiotics in improving host health and delaying the occurrence of age-related chronic diseases.