Evolution of natural lifespan variation and molecular strategies of extended lifespan in yeast

eLife

Brian M Wasko¹  Alaattin Kaya²  Lu Wang³  Theo K Bammler³  Mitchell Lee⁴  Matt Kaeberlein⁴  Xiaqing Zhao⁴  Benjamin R Harrison⁴  Daniel EL Promislow⁵  Benjamin Barre⁶  Vadim N Gladyshev⁶  Xuming Zhou⁶  Alexander Tyshkovskiy⁷  Siming Ma⁸  Cheryl Zi Jin Phua⁸  Weiqiang Liu⁹ 

[1] Department of Biology, University of Houston - Clear Lake, Houston, United States;Department of Biology, Virginia Commonwealth University, Richmond, United States;Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, United States;Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States;Department of Laboratory Medicine and Pathology, University of Washington, Seattle, United States;Department of Biology, University of Washington, Seattle, United States;Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United States;Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United States;Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russian Federation;Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore;Key Laboratory of Animal Ecology and Conservation Biology, Chinese Academy of Sciences, Institute of Zoology, Beijing, China;

关键词: aging;    natural lifespan variation;    longevity;    gene-environment interaction;    multi-omics;    yeast;    S. cerevisiae;    S. paradoxus;   

DOI  :  10.7554/eLife.64860

来源: eLife Sciences Publications, Ltd

【 摘 要 】

To understand the genetic basis and selective forces acting on longevity, it is useful to examine lifespan variation among closely related species, or ecologically diverse isolates of the same species, within a controlled environment. In particular, this approach may lead to understanding mechanisms underlying natural variation in lifespan. Here, we analyzed 76 ecologically diverse wild yeast isolates and discovered a wide diversity of replicative lifespan (RLS). Phylogenetic analyses pointed to genes and environmental factors that strongly interact to modulate the observed aging patterns. We then identified genetic networks causally associated with natural variation in RLS across wild yeast isolates, as well as genes, metabolites, and pathways, many of which have never been associated with yeast lifespan in laboratory settings. In addition, a combined analysis of lifespan-associated metabolic and transcriptomic changes revealed unique adaptations to interconnected amino acid biosynthesis, glutamate metabolism, and mitochondrial function in long-lived strains. Overall, our multiomic and lifespan analyses across diverse isolates of the same species shows how gene–environment interactions shape cellular processes involved in phenotypic variation such as lifespan.

【 授权许可】

CC BY