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. 2013 Mar 28;153(1):228–239. doi: 10.1016/j.cell.2013.02.035

Figure 6.

Figure 6

AMP kinase and SKN-1 Protect Against Biguanide Toxicity

(A) Phenformin increases pAAK-2 levels, suggesting AMPK activation (2-day-old adults).

(B) Phenformin shortens lifespan in aak-2(ok524) AMPK loss-of-function mutants.

(C) Phenformin does not extend lifespan in skn-1(zu135) mutants.

(D) AMPK-dependent induction of expression by phenformin of SKN-1-activated reporter gst-4::gfp in L4 animals.

(E) aak-2(ok524) but not daf-16(mgDf50) mutants are hypersensitive to growth inhibition by metformin, as measured by the food clearance assay.

(F) skn-1(zu135) increases sensitivity to growth inhibition by metformin.

(G) Metformin increases expression of gst-4::gfp under conditions that do not increase lifespan (maintenance on E. coli HT115).

(H) Life extension by metformin pretreatment of E. coli is partially AMPK-dependent.

(I) Life extension by metformin pretreatment of E. coli is not SKN-1-dependent.

Error bars represent SEM of at least three independent biological replicates. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001. See also Figure S6. For statistics, see Table S6.