Stabilization of HIF in mammals through loss of the E3 ubiquitin ligase von Hippel-Lindau (VHL) protein led to a disease characterized by renal carcinomas (Ivan and Kaelin 2001), whereas in C. elegans, loss of vhl-1, improved proteostasis and increased lifespan (Leiser et al. 2015). Here, VHL is linked to renal carcinoma.