Defining molecular basis for longevity traits in natural yeast isolates

Abstract

The budding yeast has served as a useful model organism in aging studies, leading to the identification of genetic determinants of longevity, many of which are conserved in higher eukaryotes. However, factors that promote longevity in a laboratory setting often have severe fitness disadvantages in the wild. To obtain an unbiased view on longevity regulation, we analyzed how a replicative lifespan is shaped by transcriptional, translational, metabolic, and morphological factors across 22 wild-type Saccharomyces cerevisiae isolates. We observed significant differences in lifespan across these strains and found that their longevity is strongly associated with up-regulation of oxidative phosphorylation and respiration and down-regulation of amino- acid and nitrogen compound biosynthesis. As calorie restriction and TOR signaling also extend the lifespan by adjusting many of the identified pathways, the data suggest that the natural plasticity of yeast lifespan is shaped by the processes that not only do not impose cost on fitness, but also are amenable to dietary intervention. A new study pinpoints a consistent set of genes and pathways underlying variations in yeast lifespan. Vadim Gladyshev at Harvard Medical School and co-workers analyzed 22 Saccharomyces cerevisiae yeast strains with diverse lifespans and habitats, looking to identify genomic signatures associated with natural variations in longevity. They observed a number of factors that characterized the longest-lived strains, including the upregulation of aerobic respiration, and found that interactions between genes and the environment were key. They also showed that factors associated with increased longevity in yeast strains do not necessarily degrade the fitness of those strains in the wild, and that longevity can be influenced through diet. The study thus paints a more complete picture of how environmental factors trigger changes—some hard–wired in the genome—that have real consequences on aging and longevity.