Understanding Aging Genes and Pathways: Insight from Yeast

Even though there is a general agreement on the heritability of longevity in humans, the complex network of genetic and non-genetic factors affecting our lifespan is far from being fully elucidated. In this context, simple model organisms can still contribute to understanding the fundamental mechanisms involved in longevity, potentially highlighting novel therapeutic targets. Studies in the yeast Saccharomyces cerevisiae, the simplest eukaryotic model system, have identified the Ras-cAMP-PKA, TOR and Sch9 pathways as pro-aging signaling cascades. Even though this unicellular fungus is evolutionarily distant from complex mammals, some of the observations made in yeast have been eventually confirmed in higher organisms, including humans. The tractability of this model organism has also enabled a detailed molecular characterization of those pathways identifying potential therapeutic targets. In addition, the molecular characterization of these nutrient-dependent pathways helps screen for molecules capable of modulating stress resistance, cellular nutrient responses and autophagy. This evolutionary conservation, spanning from fission yeast to mammals, positions this model organism as a valuable tool for screening molecules, drugs, and dietary interventions that affect longevity. Here, we describe the principal methodologies used to study aging in yeast, the major findings obtained and their translational validity in higher organisms.