Quantitative evidence for conserved longevity pathways between divergent eukaryotic species
Open Access
- 13 March 2008
- journal article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 18 (4), 564-570
- https://doi.org/10.1101/gr.074724.107
Abstract
Studies in invertebrate model organisms have been a driving force in aging research, leading to the identification of many genes that influence life span. Few of these genes have been examined in the context of mammalian aging, however, and it remains an open question as to whether and to what extent the pathways that modulate longevity are conserved across different eukaryotic species. Using a comparative functional genomics approach, we have performed the first quantitative analysis of the degree to which longevity genes are conserved between two highly divergent eukaryotic species, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Here, we report the replicative life span phenotypes for single-gene deletions of the yeast orthologs of worm aging genes. We find that 15% of these yeast deletions are long-lived. In contrast, only 3.4% of a random set of deletion mutants are long-lived—a statistically significant difference. These data suggest that genes that modulate aging have been conserved not only in sequence, but also in function, over a billion years of evolution. Among the longevity determining ortholog pairs, we note a substantial enrichment for genes involved in an evolutionarily conserved pathway linking nutrient sensing and protein translation. In addition, we have identified several conserved aging genes that may represent novel longevity pathways. Together, these findings indicate that the genetic component of life span determination is significantly conserved between divergent eukaryotic species, and suggest pathways that are likely to play a similar role in mammalian aging.Keywords
This publication has 37 references indexed in Scilit:
- Yeast Life Span Extension by Depletion of 60S Ribosomal Subunits Is Mediated by Gcn4Cell, 2008
- The Princeton Protein Orthology Database (P-POD): A Comparative Genomics Analysis Tool for BiologistsPLOS ONE, 2007
- Longevity determined by developmental arrest genes in Caenorhabditis elegansAging Cell, 2007
- Lifespan Regulation by Evolutionarily Conserved Genes Essential for ViabilityPLoS Genetics, 2007
- Ruminations on dietary restriction and agingCellular and Molecular Life Sciences, 2007
- eIF4E function in somatic cells modulates ageing in Caenorhabditis elegansNature, 2007
- Lifespan extension by conditions that inhibit translation in Caenorhabditis elegansAging Cell, 2006
- Inhibition of mRNA translation extends lifespan in Caenorhabditis elegansAging Cell, 2006
- New Genes Tied to Endocrine, Metabolic, and Dietary Regulation of Lifespan from a Caenorhabditis elegans Genomic RNAi ScreenPLoS Genetics, 2005
- Genetic analysis of ageing: role of oxidative damage and environmental stressesNature Genetics, 1996