Nrf transcription factors in stress response and epigenetic aging by Dirk Bohmann - Welcome to the next CCB seminar scheduled for Wednesday 21st of June at 13:00 hrs.

Speaker: Dirk Bohmann, Phd, University of Rochester Medical Center, Rochester, NY

Title: Nrf transcription factors in stress response and epigenetic aging

Programme

13:00 hrs: Nrf transcription factors in stress response and epigenetic aging
Speaker:  Dirk Bohmann, Phd, University of Rochester Medical Center, Rochester, NY

 

Abstract

The Drosophila cap’n’collar locus encodes leucine zipper transcriptions factor with homology to mammalian Nrf1 and Nrf2. The CncC protein activates gene expression programs that defend flies against xenobiotic and oxidative insults, as well as unfolded protein stress. Consistent with these protective functions, CncC can ameliorate pathologies that are caused or exacerbated by oxidative or unfolded proteins. We and others have demonstrated this effect in fly models for Parkinson’s and Alzheimer’s disease. Gain of CncC function can also extend lifespan, implicating the transcription factor in the control of aging. We have shown that the capacity of flies to activate the expression of CncC target genes in response to stress exposure declines with increasing age of the organism. Chromatin analyses by DNAse hypersensitive site mapping indicate that this phenotype is caused by an age-associated loss of epigenetic organization around the CncC target gene promoters. With increasing age of the organism, these transcription control regions lose their youthful open chromatin conformation and are no longer accessible for binding by activated CncC transcription factors. We have developed genetic and pharmacological strategies that prevent this epigenetic degeneration to preserve signal dependent transcriptional responses in old animals. This preservation of transcriptional competence results in increased fitness in later stages of life and extended lifespan. Our studies suggest that epigenetic degeneration is a fundamental cause of aging, Based on these findings, we present possible strategies to slow down epigenetic aging and to extend healthspan and lifespan.

Organizer

CCB by Tor Erik Rusten
Published June 7, 2017 5:52 PM - Last modified June 7, 2017 5:53 PM