Research Paper|Volume 7, Issue 3|pp 177—194

Functional genomic analysis reveals overlapping and distinct features of chronologically long-lived yeast populations

Margaret B. Wierman¹, Mirela Matecic¹, Veena Valsakumar¹, Mingguang Li¹, Daniel L. Smith Jr.^2,^3,⁴, Stefan Bekiranov¹, Jeffrey S. Smith¹

¹Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
²Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 5233, USA
³Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL 5233, USA
⁴Comprehensive Center for Healthy Aging, University of Alabama at Birmingham, Birmingham, AL 5233, USA

Received: October 6, 2014Accepted: March 5, 2015Published: March 7, 2015

https://doi.org/10.18632/aging.100729

Copyright: © 2015 Wierman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Yeast chronological lifespan (CLS) is extended by multiple genetic and environmental manipulations, including caloric restriction (CR). Understanding the common changes in molecular pathways induced by such manipulations could potentially reveal conserved longevity mechanisms. We therefore performed gene expression profiling on several long-lived yeast populations, including an ade4∆ mutant defective in de novo purine (AMP) biosynthesis, and a calorie restricted WT strain. CLS was also extended by isonicotinamide (INAM) or expired media derived from CR cultures. Comparisons between these diverse long-lived conditions revealed a common set of differentially regulated genes, several of which were potential longevity biomarkers. There was also enrichment for genes that function in CLS regulation, including a long-lived adenosine kinase mutant (ado1∆) that links CLS regulation to the methyl cycle and AMP. Genes co-regulated between the CR and ade4∆ conditions were dominated by GO terms related to metabolism of alternative carbon sources, consistent with chronological longevity requiring efficient acetate/acetic acid utilization. Alternatively, treating cells with isonicotinamide (INAM) or the expired CR media resulted in GO terms predominantly related to cell wall remodeling, consistent with improved stress resistance and protection against external insults like acetic acid. Acetic acid therefore has both beneficial and detrimental effects on CLS.