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. 2023 Aug 22;12:e82210. doi: 10.7554/eLife.82210

Figure 3. Peroxisomal protein import, fatty acid elongases, and fatty acid desaturases are required for the pro-longevity effects of biguanides.

Figure 3.

(A–B) Knockdown of prx-5 (A) and prx-19 (B) by RNA interference (RNAi) eliminates or significantly suppresses phenformin-mediated lifespan extension. (C) Schematic representation of the mono- (MUFA) and polyunsaturated fatty acid (PUFA) synthesis pathway in C. elegans (adapted from Figure 1 of Watts, 2016). (D–G) RNAi of two fatty acid desaturases (D–E) and two fatty acid elongases (F and G) involved in the synthesis of 18- and 20-carbon PUFAs blunt phenformin-mediated lifespan extension in wild-type worms. Colored symbols for elo and fat genes (vs. those in black and white) in (C) indicates those that inhibit phenformin lifespan extension when knocked down by RNAi. For (A, B) and (D–G), results are representative of two to three biological replicates. **, p<0.01; ***, p<0.001; ****, p<0.0001 by log-rank analysis. Note that (D–G) contain the same wild-type controls as they are visualized from the same replicate of the study. See also Supplementary file 1 for tabular survival data and biological replicates.