Proceedings of the National Academy of Sciences · 2009 · 64 citations · 20 references
Life SciencesMolecular BiologyPhysiologyAgingGene ExpressionTranscriptional RegulationAging PhysiologyHypoxia AdaptationLung DevelopmentMitochondrial SignalingRespiratory PathophysiologyRespiratory PhysiologyC. Elegans Developmental ModelsCaenorhabditis Elegans Zygotic AsymmetryHypercapnia PhysiologyLife Span ExtensionLung DiseasesMitochondrial PathwaysMuscle Tissue OrganizationRespiratory Adaptations
Hypercapnia (high CO(2) levels) occurs in a number of lung diseases and it is associated with worse outcomes in patients with chronic obstructive lung disease (COPD). However, it is largely unknown how hypercapnia is sensed and responds in nonneuronal cells. Here, we used C. elegans to study the response to nonanesthetic CO(2) levels and show that levels exceeding 9% induce aberrant motility that is accompanied by age-dependent deterioration of body muscle organization, slowed development, reduced fertility and increased life span. These effects occur independently of the IGF-R, dietary restriction, egg laying or mitochondrial-induced aging pathways. Transcriptional profiling analysis shows specific and dynamic changes in gene expression after 1, 6, or 72 h of exposure to 19% CO(2) including increased transcription of several 7-transmembrane domain and innate immunity genes and a reduction in transcription of many of the MSP genes. Together, these results suggest specific physiological and molecular responses to hypercapnia, which appear to be independent of early heat shock and HIF mediated pathways.
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THE GENETICS OF <i>CAENORHABDITIS ELEGANS</i>
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