Protein-repair and hormone-signaling pathways specify dauer and adult longevity and dauer development in Caenorhabditis elegans.
Protein damage that accumulates during aging can be mitigated by a repair methyltransferase, the l-isoaspartyl-O-methyltransferase. In Caenorhabditis elegans, the pcm-1 gene encodes this enzyme. In response to pheromone, we show that pcm-1 mutants form fewer dauer larvae with reduced survival due to loss of the methyltransferase activity. Mutations in daf-2, an insulin/insulin-like growth factor-1-like receptor, and daf-7, a transforming growth factor-beta-like ligand, modulate pcm-1 dauer defects. Additionally, daf-2 and daf-7 mutant dauer larvae live significantly longer than wild type. Although dauer larvae are resistant to many environmental stressors, a proportionately larger decrease in dauer larvae life spans occurred at 25 degrees C compared to 20 degrees C than in adult life span. At 25 degrees C, mutation of the daf-7 or pcm-1 genes does not change adult life span, whereas mutation of the daf-2 gene and overexpression of PCM-1 increases adult life span. Thus, there are both overlapping and distinct mechanisms that specify dauer and adult longevity.
Banfield
Kelley L
KL
Department of Cellular and Structural Biology, University of Texas Science Center at San Antonio, San Antonio, TX 78229, USA.
Gomez
Tara A
TA
Lee
Wendy
W
Clarke
Steven
S
Larsen
Pamela L
PL
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D004843:Epistasis, Genetic; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D017238:Genes, Helminth; D007814:Larva / Q000502:physiology; D008136:Longevity / Q000235:genetics / Q000502:physiology; D008780:Methyltransferases / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D010675:Pheromones; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase / Q000235:genetics; D011972:Receptor, Insulin / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C102095:DAF-7 protein, C elegans; D051858:Forkhead Transcription Factors; C507738:HIM-8 protein, C elegans; D010675:Pheromones; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C108831:daf-16 protein, C elegans; C490112:pcm-1 protein, C elegans; D008780:Methyltransferases; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin
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