The von Hippel Lindau tumor suppressor limits longevity.
Many genes are responsible for the modulation of lifespan in model organisms. In addition to regulating adaptive biologic responses that control stress signaling and longevity, some of these genes participate in tumor formation. The mechanisms that determine longevity and link regulation of lifespan with tumorigenesis are poorly understood. Here, we show that the tumor suppressor von Hippel-Lindau (VHL), which has widely known roles in renal carcinogenesis and the formation of kidney cysts, controls longevity in Caenorhabditis elegans. Loss of vhl-1 significantly increased lifespan and resulted in accelerated basal signaling of the p38 mitogen-activated protein kinase PMK-3. Furthermore, the VHL-1 effect on the regulation of lifespan was independent of the insulin/IGF-1-like signaling pathway, suggesting a mechanism for stress resistance that controls both lifespan and tumorigenesis. These findings define VHL-1 as a player in longevity signaling and connect aging, regulation of lifespan, and stress responses with formation of renal cell carcinomas.
Müller
Roman-Ulrich
RU
Renal Division, Department of Medicine, University of Cologne, Kerpener Strasse 62, Cologne, Germany.
Fabretti
Francesca
F
Zank
Sibylle
S
Burst
Volker
V
Benzing
Thomas
T
Schermer
Bernhard
B
D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000502:physiology; D008136:Longevity / Q000235:genetics* / Q000502:physiology; D020935:MAP Kinase Signaling System; D034622:RNA Interference; D015398:Signal Transduction; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein