Inhibition of a eukaryotic initiation factor (eIF2Bdelta/F11A3.2) during adulthood extends lifespan in Caenorhabditis elegans.
The critical role of protein synthesis in regulating lifespan has been evidenced. This study shows that adult-onset RNAi inactivation of eukaryotic initiation factor 2Bdelta (eIF2Bdelta/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. (35)S-methionine incorporation assay showed that global protein synthesis is reduced by eIF2Bdelta/F11A3.2 RNAi. Inhibition of eIF2Bdelta/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 eIF2Bdelta/F11A3.2 RNAi is suppressed in FOXO transcription factor daf-16 deletion mutants. Adult-onset eIF2Bdelta/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 eIF2Bdelta/F11A3.2 RNAi in daf-16 mutants reduced fecundity, but did not extend lifespan. Furthermore, adult-onset eIF2Bdelta/F11A3.2 RNAi did not extend the lifespan of germline-defective glp-4 organisms. Thus, it is possible that eIF2Bdelta/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
Daisuke
D
Department of Neurobiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Yamaguchi
Atsushi
A
Yamashita
Toshihide
T
D000375:Aging / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D020717:Eukaryotic Initiation Factor-2B / Q000037:antagonists & inhibitors*; D005298:Fertility / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental; D008136:Longevity / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D034622:RNA Interference
D029742:Caenorhabditis elegans Proteins; D020717:Eukaryotic Initiation Factor-2B