TY - JOUR
T1 - Elevated CO2 levels affect development, motility, and fertility and extend life span in Caenorhabditis elegans
AU - Sharabi, Kfir
AU - Hurwitz, Anat
AU - Simon, Amos J.
AU - Beitel, Greg J.
AU - Morimoto, Richard I.
AU - Rechavi, Gideon
AU - Sznajder, Jacob I.
AU - Gruenbaum, Yosef
PY - 2009/3/10
Y1 - 2009/3/10
N2 - Hypercapnia (high CO2 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 CO2 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% CO2 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.
AB - Hypercapnia (high CO2 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 CO2 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% CO2 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.
KW - Aging
KW - Gene expression
KW - Hypercapnia
KW - Muscle deterioration
KW - Physiology
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U2 - 10.1073/pnas.0900309106
DO - 10.1073/pnas.0900309106
M3 - Article
C2 - 19237558
AN - SCOPUS:62649116368
SN - 0027-8424
VL - 106
SP - 4024
EP - 4029
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 10
ER -