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This Article Full Text Free Full Text (PDF) Free Supplemental Data All Versions of this Article: fj.08-112953v1 22/12/4327    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tohyama, D. Articles by Yamashita, T. Search for Related Content PubMed PubMed Citation Articles by Tohyama, D. Articles by Yamashita, T.

Inhibition of a eukaryotic initiation factor (eIF2B/F11A3.2) during adulthood extends lifespan in Caenorhabditis elegans

Daisuke Tohyama^*, Atsushi Yamaguchi^*,1 and Toshihide Yamashita^*,

^* Department of Neurobiology, Graduate School of Medicine, Chiba University, Chiba, Japan; and

Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan

¹Correspondence: Department of Neurobiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. E-mail: atsyama{at}restaff.chiba-u.jp

The critical role of protein synthesis in regulating lifespan has been evidenced. This study shows that adult-onset RNAi inactivation of eukaryotic initiation factor 2B (eIF2B/F11A3.2), a subunit of eIF2B, extends the mean lifespan of Caenorhabditis elegans. eIF2B is a GDP-GTP exchange factor for eIF2—a rate-limiting factor for protein synthesis initiation. ³⁵S-methionine incorporation assay showed that global protein synthesis is reduced by eIF2B/F11A3.2 RNAi. Inhibition of eIF2B/F11A3.2 during adulthood conferred thermal and oxidative stress resistance and reduced the fecundity and fat storage, suggesting the possible trade-offs of resources between reproduction and somatic maintenance. Lifespan extension by adult-onset eIF2B/F11A3.2 RNAi is suppressed in FOXO transcription factor daf-16 deletion mutants. Adult-onset eIF2B/F11A3.2 RNAi increases the expression of stress-resistant genes, including hsp-16.2, hsp-70, hsp90, and sod-3, some of which are reported to be targets of DAF-16. Adult-onset eIF2B/F11A3.2 RNAi in daf-16 mutants reduced fecundity, but did not extend lifespan. Furthermore, adult-onset eIF2B/F11A3.2 RNAi did not extend the lifespan of germline-defective glp-4 organisms. Thus, it is possible that eIF2B/F11A3.2 RNAi during adulthood prolongs lifespan via daf-16, which induces stress resistance in organisms. This might be the mechanism, at least in part, for trade-offs of resources between reproduction and somatic maintenance.—Tohyama, D., Yamaguchi, A., Yamashita, T. Inhibition of a eukaryotic initiation factor (eIF2B/F11A3.2) during adulthood extends lifespan in Caenorhabditis elegans.

Key Words: aging • daf-16