Activation of DAF-16/FOXO by reactive oxygen species contributes to longevity in long-lived mitochondrial mutants in Caenorhabditis elegans.

Autor: Megan M Senchuk, Dylan J Dues, Claire E Schaar, Benjamin K Johnson, Zachary B Madaj, Megan J Bowman, Mary E Winn, Jeremy M Van Raamsdonk
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: PLoS Genetics, Vol 14, Iss 3, p e1007268 (2018)
Druh dokumentu: article
ISSN: 1553-7390
1553-7404
DOI: 10.1371/journal.pgen.1007268
Popis: Mild deficits in mitochondrial function have been shown to increase lifespan in multiple species including worms, flies and mice. Here, we study three C. elegans mitochondrial mutants (clk-1, isp-1 and nuo-6) to identify overlapping genetic pathways that contribute to their longevity. We find that genes regulated by the FOXO transcription factor DAF-16 are upregulated in all three strains, and that the transcriptional changes present in these worms overlap significantly with the long-lived insulin-IGF1 signaling pathway mutant daf-2. We show that DAF-16 and multiple DAF-16 interacting proteins (MATH-33, IMB-2, CST-1/2, BAR-1) are required for the full longevity of all three mitochondrial mutants. Our results suggest that the activation of DAF-16 in these mutants results from elevated levels of reactive oxygen species. Overall, this work reveals an overlapping genetic pathway required for longevity in three mitochondrial mutants, and, combined with previous work, demonstrates that DAF-16 is a downstream mediator of lifespan extension in multiple pathways of longevity.
Databáze: Directory of Open Access Journals
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