Figure 5.

Effect of Metformin on the Methionine Cycle but Not the Folate Cycle in C elegans

(A) Effect of metformin on C. elegans/E. coli system: little effect on nematode folate homeostasis.

(B) Metformin induces a shift toward shorter-chain (n = 1–3) glutamate folate forms in C. elegans.

(C) Metformin increases S-adenosylmethionine (SAMe) levels in E. coli (OP50).

(D) Mutation of metr-1(ok521) (methionine synthetase, MS) increases lifespan only in the presence of metformin.

(E) In C. elegans, metformin greatly reduces SAMe levels and increases S-adenosylhomocysteine (SAH) levels.

(F) Metformin shortens lifespan in S-adenosylmethionine synthase-deficient sams-1(ok3033) mutants.

Error bars represent SEM. ^∗p < 0.05; ^∗∗p < 0.01; ^∗∗∗p < 0.001. See also Figure S5. For statistics, see Table S5.