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Comments on Bharill, P et al. (2013) International Worm Meeting "Modulation of HIF-1 activity and its effect on stress tolerance and longevity in C. elegans." (0)
Overview
Bharill, P, Fabretti, F, Gharbi, H, Schermer, B, Benzing, T, & Mueller, R (2013). Modulation of HIF-1 activity and its effect on stress tolerance and longevity in C. elegans presented in International Worm Meeting. Unpublished information; cite only with author permission.
While stabilization of HIF-1a can lead to tumor formation in mammals, activation of its worm orthologue HIF-1 extends lifespan. HIF-1a plays a central role in the cellular response to varying oxygen levels. While in worms, hypoxia leads to longevity and increased stress resistance by activation of HIF-1, in mammals ischemic or hypoxic preconditioning can be exploited to protect organ integrity from a row of damaging stimuli. These findings hold the promise to provide us with novel approaches to also prevent organ failure in the clinical setting of patients being exposed to toxic therapies or ischemic damage. For being able to exploit these findings in an optimal way a better understanding of the underlying molecular mechanisms will be of utmost importance. Due to its simple maintenance and easy genetic amenability C. elegans is the perfect model to study the molecular basics behind the increase in cellular stress resistance underlying the effects of preconditioning. Using gene expression profiling coupled to differential stress testing after activation of hypoxia signaling we are trying to unravel the key players involved. Doing so will not only extend our understanding of the hypoxia pathway in longevity and cellular stress resistance but may also yield a putative list of targets that can be tested in mouse models of organ preconditioning.
Affiliation:
- Department 2 of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.