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加利利盲鼹鼠转录组对缺氧的适应性可能是其具有长寿和抗癌能力等复杂表型的基础。

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

作者信息

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

机构信息

Molecular Genetics & Genome Analysis, Institute of Organismic and Molecular Evolution, Faculty of Biology, Johannes Gutenberg-University, Mainz, Germany.

Nucleic Acids Core Facility, Faculty of Biology, Johannes Gutenberg-University, Mainz, Germany.

出版信息

NPJ Aging. 2025 Mar 6;11(1):16. doi: 10.1038/s41514-025-00206-3.

DOI:10.1038/s41514-025-00206-3
PMID:40044716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11882797/
Abstract

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.

摘要

在地下啮齿动物加利利盲鼹鼠（(Nanno)spalax galili）中，对缺氧的进化适应与长寿和肿瘤抗性相关。盲鼹鼠适应的基因调控网络可能会找出人类保持健康的策略。通过比较盲鼹鼠和大鼠在缺氧和常氧条件下肝脏、肾脏和脾脏的转录组数据，我们确定了两个物种多个器官共有的差异表达基因途径。种间全身差异影响细胞死亡、抗氧化防御、DNA修复、能量代谢、免疫反应和血管生成等过程，这些过程可能在盲鼹鼠对环境缺氧的适应中起关键作用。在所有器官中，与大鼠相比，盲鼹鼠中维持基因组稳定性和DNA修复的基因转录水平升高，同时有氧能量代谢和促炎基因的表达降低。这些转录组变化可能解释了盲鼹鼠非凡的寿命及其抗癌能力。所确定的基因网络为进一步研究盲鼹鼠复杂表型背后的分子基础提供了候选对象。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/216e/11882797/3c4588fc4a49/41514_2025_206_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/216e/11882797/0fb2030fb145/41514_2025_206_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/216e/11882797/d2f777b35ab6/41514_2025_206_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/216e/11882797/e7b3e461cb3e/41514_2025_206_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/216e/11882797/3506de71b8ed/41514_2025_206_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/216e/11882797/02aeb2d8a995/41514_2025_206_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/216e/11882797/835c0e4e61a3/41514_2025_206_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/216e/11882797/9dff222d1992/41514_2025_206_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/216e/11882797/cdecd023a1ea/41514_2025_206_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/216e/11882797/20a7fc53a900/41514_2025_206_Fig12_HTML.jpg

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