Title Page
Contents
ABSTRACT 8
Introduction 10
1. Gut microbes 11
2. C. elegans 12
3. C. elegans and gut microbes 14
4. H-NS and methylglyoxal 20
5. Aims of the study 23
Materials and Methods 24
1. Lifespan screening 25
2. E. coli strain 26
3. C. elegans 26
4. Lifespan assay 27
5. Thrashing assay 28
6. Measurement of growth rate 28
7. Brood size assay 29
8. Thermotolerance assay 29
9. Dauer assay 29
10. Quantification of Methylglyoxal using HPLC 30
Results 32
1. Genetic regulation of longevity on gut microbes - host interspecies 33
2. hns mutant E. coli extends not only lifespan but also health span. 38
3. hns mutant E. coli extends the lifespan of C. elegans via DAF-16/FOXO. 44
4. Bacteria-derived methylglyoxal modulates the lifespan of host. 50
5. Bacteria-derived metabolite MG regulates the lifespan of C. elegans through DAF-16/FOXO. 55
Discussion 60
Reference 64
국문 초록 67
Table 1. hns mutant E. coli promotes longevity in C. elegans. 40
Table 2. hns mutant E. coli enhanced the thermotolerance of C. elegans in a... 43
Table 3. Relative survival rate of C. elegans mutants fed hns mutant E. coli. 46
Table 4. hns mutant E. coli extends the lifespan of C. elegans via DAF-... 49
Table 5. Bacteria-derived metabolite MG modulates host longevity. 53
Table 6. The lifespan extension by hns mutant E. coli was completely... 54
Table 7. Bacteria-derived metabolite MG regulates the lifespan of C. elegans... 57
Table 8. DAF-16/FOXO is required for lifespan modulation by MG... 59
Figure 1. Lifecycle of C. elegans at 22℃. 13
Figure 2. Effects of aroD deletion on the biosynthesis of shikimic acid and... 16
Figure 3. Schematic diagram of inhibition of folate biosynthesis pathway of... 17
Figure 4. Schematic diagram of folate and methionine cycle 19
Figure 5. Schematic diagram of the main metabolic pathways involved MG... 22
Figure 6. Schematic diagram of the genome-wide lifespan screens. 35
Figure 7. The diverse genetic background of E. coli regulate the lifespan of C.elegans. 36
Figure 8. Genetic background of gut microbes is a bona fide regulator of host longevity. 37
Figure 9. hns mutant E. coli extends lifespan of wild type N2 C. elegans. 39
Figure 10. hns mutant E. coli is beneficial to health span of C. elegans. 42
Figure 11. hns mutant E. coli extends the lifespan of C. elegans via DAF-... 48
Figure 12. Bacteria-derived metabolite MG modulates host longevity. 52
Figure 13. Bacteria-derived metabolite MG regulates the lifespan of C. elegans... 56
Figure 14. DAF-16/FOXO is required for lifespan modulation by MG... 58