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<p>In the subterranean rodent <i>(Nanno)spalax galili</i>, evolutionary adaptation to hypoxia is correlated with longevity and tumor resistance. Adapted gene-regulatory networks of <i>Spalax</i> might pinpoint strategies to maintain health in humans. Comparing liver, kidney and spleen transcriptome data from <i>Spalax</i> and rat at hypoxia and normoxia, we identified differentially expressed gene pathways common to multiple organs in both species. Body-wide interspecies differences affected processes like cell death, antioxidant defense, DNA repair, energy metabolism, immune response and angiogenesis, which may play a crucial role in <i>Spalax</i>’s adaptation to environmental hypoxia. In all organs, transcription of genes for genome stability maintenance and DNA repair was elevated in <i>Spalax</i> versus rat, accompanied by lower expression of aerobic energy metabolism and proinflammatory genes. These transcriptomic changes might account for the extraordinary lifespan of <i>Spalax</i> and its cancer resistance. The identified gene networks present candidates for further investigating the molecular basis underlying the complex <i>Spalax</i> phenotype.</p>

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Adaptation of the Spalax galili transcriptome to hypoxia may underlie the complex phenotype featuring longevity and cancer resistance

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月6日

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  • Gesa Poetzsch,
  • Luca Jelacic,
  • Leon Dammer,
  • Sören Lukas Hellmann,
  • Michelle Balling,
  • Miguel Andrade-Navarro,
  • Aaron Avivi,
  • Imad Shams,
  • Anne Bicker,
  • Thomas Hankeln

摘要

In the subterranean rodent (Nanno)spalax galili, evolutionary adaptation to hypoxia is correlated with longevity and tumor resistance. Adapted gene-regulatory networks of Spalax might pinpoint strategies to maintain health in humans. Comparing liver, kidney and spleen transcriptome data from Spalax and rat at hypoxia and normoxia, we identified differentially expressed gene pathways common to multiple organs in both species. Body-wide interspecies differences affected processes like cell death, antioxidant defense, DNA repair, energy metabolism, immune response and angiogenesis, which may play a crucial role in Spalax’s adaptation to environmental hypoxia. In all organs, transcription of genes for genome stability maintenance and DNA repair was elevated in Spalax versus rat, accompanied by lower expression of aerobic energy metabolism and proinflammatory genes. These transcriptomic changes might account for the extraordinary lifespan of Spalax and its cancer resistance. The identified gene networks present candidates for further investigating the molecular basis underlying the complex Spalax phenotype.