title: PCH-2 regulates Caenorhabditis elegans lifespan.
abstract: Components or downstream targets of many signaling pathways such as Insulin/IGF-1 and TOR, as well as genes involved in cellular metabolism and bioenergetics can extend worm lifespan 20% or more. The C. elegans gene pch-2 and its homologs, including TRIP13 in humans, have been studied for their functions in cell mitosis and meiosis, but have never been implicated in lifespan regulation. Here we show that over-expression of TRIP13 in human fibroblasts confers resistance to environmental stressors such as UV radiation and oxidative stress. Furthermore, pch-2 overexpression in C. elegans extends worm lifespan, and enhances worm survival in response to various stressors. Conversely, reducing pch-2 expression with RNAi shortens worm lifespan. Additional genetic epistasis analysis indicates that the molecular mechanism of pch-2 in worm longevity is tied to functions of the sirtuin family, implying that pch-2 is another chromatin regulator for worm longevity. These findings suggest a novel function of the pch-2 gene involved in lifespan determination.
authors: Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Hong
authors: H
authors: Qian
authors: Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Xiangru
authors: X
authors: Xu
authors: Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06520, USA.|Department of Biomedical Engineering, Yale University, New Haven,CT 06520, USA.
authors: Laura E
authors: LE
authors: Niklason
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly; D004843:Epistasis, Genetic; D005347:Fibroblasts / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008136:Longevity; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D034622:RNA Interference; D011859:Radiography; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014466:Ultraviolet Rays; D055815:Young Adult
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C000599595:PCH-2 protein, C elegans; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C575259:TRIP13 protein, human; C523791:Trip13 protein, mouse
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