Co-chaperone p23 Regulates <i>C</i>. <i>elegans</i> Lifespan in Response to Temperature

<div><p>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, <i>daf-41</i>/ZC395.10, the <i>C</i>. <i>elegans</i> homolog of p23 co-chaperone/prostaglandin E synthase-3, governs entry into the long-lived dauer diapause and regulates adult lifespan. <i>daf-41</i> deletion triggers constitutive entry into the dauer diapause at elevated temperature dependent on neurosensory machinery (<i>daf-10/IFT122</i>), insulin/IGF-1 signaling (<i>daf-16</i>/FOXO), and steroidal signaling (<i>daf-12</i>/FXR). Surprisingly, <i>daf</i>-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 <i>daf-16</i>/FOXO and heat shock factor <i>hsf-1</i>, while short lived phenotypes converge on <i>daf-16</i>/FOXO and depend on the <i>daf-12</i>/FXR steroid receptor. Correlatively <i>daf-41</i> affected expression of DAF-16 and HSF-1 target genes at high temperature, and nuclear extracts from <i>daf-41</i> animals showed increased occupancy of the heat shock response element. Our studies suggest that <i>daf-41</i>/p23 modulates key transcriptional changes in longevity pathways in response to temperature.</p>