title: Co-chaperone p23 regulates C. elegans Lifespan in Response to Temperature.
abstract: Temperature potently modulates various physiologic processes including organismal motility, growth rate, reproduction, and ageing. In ectotherms, longevity varies inversely with temperature, with animals living shorter at higher temperatures. Thermal effects on lifespan and other processes are ascribed to passive changes in metabolic rate, but recent evidence also suggests a regulated process. Here, we demonstrate that in response to temperature, daf-41/ZC395.10, the C. elegans homolog of p23 co-chaperone/prostaglandin E synthase-3, governs entry into the long-lived dauer diapause and regulates adult lifespan. daf-41 deletion triggers constitutive entry into the dauer diapause at elevated temperature dependent on neurosensory machinery (daf-10/IFT122), insulin/IGF-1 signaling (daf-16/FOXO), and steroidal signaling (daf-12/FXR). Surprisingly, daf-41 mutation alters the longevity response to temperature, living longer than wild-type at 25°C but shorter than wild-type at 15°C. Longevity phenotypes at 25°C work through daf-16/FOXO and heat shock factor hsf-1, while short lived phenotypes converge on daf-16/FOXO and depend on the daf-12/FXR steroid receptor. Correlatively daf-41 affected expression of DAF-16 and HSF-1 target genes at high temperature, and nuclear extracts from daf-41 animals showed increased occupancy of the heat shock response element. Our studies suggest that daf-41/p23 modulates key transcriptional changes in longevity pathways in response to temperature.
authors.affiliation: Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Makoto
authors.initials: M
authors.lastname: Horikawa
authors.affiliation: University of Michigan, Department of Internal Medicine, Division of Geriatric and Palliative Medicine, Ann Arbor, Michigan, United States of America; University of Michigan, Department of Molecular and Integrative Physiology, Ann Arbor, Michigan, United States of America.
authors.forename: Surojit
authors.initials: S
authors.lastname: Sural
authors.affiliation: University of Michigan, Department of Internal Medicine, Division of Geriatric and Palliative Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Ao-Lin
authors.initials: AL
authors.lastname: Hsu
authors.affiliation: Max Planck Institute for Biology of Ageing, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Ageing Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Department of Molecular and Cellular Biology, Huffington Center on Ageing, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Adam
authors.initials: A
authors.lastname: Antebi
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008136:Longevity; D000071876:Prostaglandin-E Synthases; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C514940:Daf-10 protein, C elegans; D051858:Forkhead Transcription Factors; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases
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