The protein kinase MBK-1 contributes to lifespan extension in daf-2 mutant and germline-deficient Caenorhabditis elegans

• Published in: Aging (Albany, NY.) NY.), 2017-05, Vol.9 (5), p.1414-1432
• Main Authors: Mack, Hildegard I D, Zhang, Peichuan, Fonslow, Bryan R, Yates, John R
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Caenorhabditis elegans - enzymology; Caenorhabditis elegans - genetics; Caenorhabditis elegans - growth & development; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene Expression Regulation; Genotype; Longevity - genetics; Mutation; Phenotype; Phosphorylation; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; Receptors, Notch - genetics; Receptors, Notch - metabolism; Research Paper; Time Factors
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.101244

In , reduction of insulin/IGF-1 like signaling and loss of germline stem cells both increase lifespan by activating the conserved transcription factor DAF-16 (FOXO). While the mechanisms that regulate DAF-16 nuclear localization in response to insulin/IGF-1 like signaling are well characterized, the molecular pathways that act in parallel to regulate DAF-16 transcriptional activity, and the pathways that couple DAF-16 activity to germline status, are not fully understood at present. Here, we report that inactivation of MBK-1, the ortholog of the human FOXO1-kinase DYRK1A substantially shortens the prolonged lifespan of and mutant animals while decreasing wild-type lifespan to a lesser extent. On the other hand, lifespan-reduction by mutation of the MBK-1-related kinase HPK-1 was not preferential for long-lived mutants. Interestingly, loss still allowed for DAF-16 nuclear accumulation but reduced expression of certain DAF-16 target genes in germline-less, but not in mutant animals. These findings indicate that and functionally interact in the germline- but not in the pathway. Together, our data suggest as a novel regulator of longevity upon both, germline ablation and DAF-2 inhibition, and provide evidence for regulating DAF-16 activity in germline-deficient animals.