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. 2021 Jun 9;12:3486. doi: 10.1038/s41467-021-23856-9

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© The Author(s) 2021, corrected publication 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — a Schematic of the methionine cycle. b, c Quantitation of methionine cycle intermediates using targeted mass spectrometry in dhfr-1i and luci, with or without FA and 5MTHF supplementation (day 1 adult). dhfr-1i decreases methionine and S-adenosyl methionine levels and increases homocysteine and adenosyl-homocysteine levels. This increase is reversed by supplementation with 5MTHF. d dhfr-1i and metr-1i. show similar regulation of mRNA expression of selected genes implicated in methionine restriction (dgn-1, let-23, ign-3, dapk-1, and daf-18), day 1 adults. e Methionine restriction specific gene signature is increased by dhfr-1i and reversed by 5MTHF supplementation, day 1 adults. f Methionine supplementation (20 mM, 40 mM) suppresses dhfr-1i longevity. b, c N = 5 independent biological replicates. d, e N = 3 independent biological replicates. f n = 150 worms per repeat per condition, N = 3 biological replicates. b–e Significance was assessed using one-way anova with Dunnett’s multiple comparisons test *p < 0.5, **p < 0.01, ***p < 0.001. f Statistics were performed with the two-sided Mantel–Cox log-rank test. *p < 0.5, **p < 0.01, ***p < 0.001. Data are presented as mean ± S.D. (Supplementary Table 8 for statistics).