Analysis Of The Effect Of Mannose On The Lifespan Of Caenorhabditis Elegans And The Underlying Mechanism

The global population is aging,which will threaten the economic growth and social sustainable development.There is emerging research on aging and related interventions.Caenorhabditis elegans is a classic model organism to study aging.In addition to its simple culture conditions in the laboratory,most of its signaling pathways are highly conserved in humans.Among its nearly 20,000 protein-coding genes,60-80% genes are highly conserved in human.Mannose is an isomer of glucose and is transported by the same transporter.Mannose is often used as a non-antibiotic treatment for recurrent human urinary tract infections.Mannose has also been shown to inhibit tumor growth,and counteract obesity caused by high-fat diet by changing the composition of intestinal microbes.However,the role of mannose in longevity has not been reported yet.Here,we used Caenorhabditis elegans as a model organism,to investigate the effect of mannose on the lifespan.Using nematode RNAi methods,RT-PCR,RNA-seq and other experimental method,we explored the possible mechanism for how mannose change the lifespan of Caenorhabditis elegans.The following are results we obtained in this thesis.(1)For the lifespan,1 mM,2.5 mM,5 mM,10 mM mannose can significantly prolong the lifespan of Caenorhabditis elegans,with 5 mM having the most pronounced effect.By feeding Caenorhabditis elegans with the stagnant Escherichia coli OP50,we confirmed that it is mannose but not its metabolites by Escherichia coli extends the lifespan.(2)For the healthy lifespan,we examined the exercise ability and fecundity of Caenorhabditis elegans.Our data showed that mannose treatment significantly improved the exercise ability of Caenorhabditis elegans.The effect of Caenorhabditis elegans in M9 buffer droplets is used.Assessed by the number of swings,at different days,mannose treatment significantly improved the nematode movement ability compared to that of the group.Regarding fecundity,there was no significant difference between mannose-treated group and the control group.(3)In order to find out the related pathways and key genes for mannose to extends C.elegans.we screened some classic mutants that affect aging,and found that the akt-1 and aak-2 mutants were added with mannose for lifespan experiments and the results were similar to wild-type C.elegans.Indicating that AKT-1 and AAK-2 did not participate in the metabolic pathways of mannose to extend the lifespan of C.elegans.(4)By analyzing the RNA-seq data of the mannose-treated experimental group and the control group,we found that mannose improved the ability of Caenorhabditis elegans to respond to heat stress.Mannose up-regulates the expression of FOXO transcription factors DAF-16,HSF-1 and HSP(heat shock protein)related genes.Using q-RT-PCR,we further confirmed that mannose significantly induced the expression of genes related to longevity.By knocking downing these genes using nematode RNAi vectors,we found that mannose prolonged the lifespan of nematodes dependent on DAF-16,HSF-1,and HSP-70.In addition,knockdown the expression of DAF-16 abolished mannose-induced transcription of HSF-1 and HSP-70.Together,our research reveals that mannose can extend the lifespan of Caenorhabditis elegans and improve its exercise capacity.Mannose extends lifespan by activating DAF-16 and heat shock proteins.These results provide a certain research basis for the further development of mannose as a drug for aging or intervening related diseases.