Wide-scale comparative analysis of longevity genes and interventions

Hagai Yanai, Arie Budovsky, Thomer Barzilay, Robi Tacutu, Vadim E. Fraifeld

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Hundreds of genes, when manipulated, affect the lifespan of model organisms (yeast, worm, fruit fly, and mouse) and thus can be defined as longevity-associated genes (LAGs). A major challenge is to determine whether these LAGs are model-specific or may play a universal role as longevity regulators across diverse taxa. A wide-scale comparative analysis of the 1805 known LAGs across 205 species revealed that (i) LAG orthologs are substantially overrepresented, from bacteria to mammals, compared to the entire genomes or interactomes, and this was especially noted for essential LAGs; (ii) the effects on lifespan, when manipulating orthologous LAGs in different model organisms, were mostly concordant, despite a high evolutionary distance between them; (iii) LAGs that have orthologs across a high number of phyla were enriched in translational processes, energy metabolism, and DNA repair genes; (iv) LAGs that have no orthologs out of the taxa in which they were discovered were enriched in autophagy (Ascomycota/Fungi), G proteins (Nematodes), and neuroactive ligand–receptor interactions (Chordata). The results also suggest that antagonistic pleiotropy might be a conserved principle of aging and highlight the importance of overexpression studies in the search for longevity regulators.

Original languageEnglish
Pages (from-to)1267-1275
Number of pages9
JournalAging Cell
Volume16
Issue number6
DOIs
StatePublished - 1 Dec 2017

Keywords

  • comparative analysis
  • evolutionary conservation
  • gene enrichment
  • gene orthology
  • longevity genes
  • proteome
  • public and private mechanisms of aging/longevity

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