UW Pathology Presents “Greatly increased lifespan by chemical tRNA synthetase inhibition via GCN4 / atf-5 / ATF-4 signaling"
 

Mark McCormick, PhD
Assistant Professor, Department of Biochemistry and Molecular Biology
University of New Mexico Health Sciences Center
Autophagy, Inflammation, and Metabolism Center of Biomedical Research Excellence

Why Attend this Seminar? 
 

Deletion of genes encoding ribosomal proteins extends replicative lifespan in yeast. This increases translation of the functionally conserved transcription factor Gcn4, and lifespan extension in these mutants is largely GCN4-dependent. Gcn4 is also translationally upregulated by uncharged tRNAs, as are its C. elegans and mammalian functional orthologs, ATF-4 and ATF4 respectively. This talk will describe data showing that chemical tRNA synthetase inhibitors upregulate Gcn4 translation, and extend yeast lifespan in a Gcn4-dependent manner. We also show that tRNA synthetase inhibitors greatly extend lifespan in C. elegans, and this depends completely on atf-4, the worm functional ortholog of GCN4. These findings establish GCN4 orthologs as conserved longevity factors and, as several types of long-lived mice exhibit elevated ATF4, they leave open the possibility that chemical inhibition of tRNA synthetases also extends lifespan in mammals.

Biography.

Mark McCormick, Assistant Professor, University of New Mexico Health Sciences Center. The McCormick Lab studies the basic biology of aging. We use multiple model systems to look for conserved biology that will help us understand and delay aging, and the onset of age-related diseases, in humans. Mark McCormick received his PhD in Biochemistry and Molecular Biology from the University of California, San Francisco, and his BS in Biology and BS in Mechanical Engineering from the University of Texas at Austin.
 

Meeting ID: 994 1137 3399
Passcode: 5202122