Naked mole rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles (genetic data)

The naked mole-rat Heterocephalus glaber is a eusocial mammal exhibiting extreme longevity (37-year lifespan), extraordinary resistance to hypoxia and absence of cardiovascular disease. To identify the mechanisms behind these exceptional traits, metabolomics and RNAseq of cardiac tissue from naked mole-rats were compared to other African mole-rat genera. We identified metabolic and genetic adaptations unique to naked mole-rats including elevated glycogen, thus enabling glycolytic ATP generation during cardiac ischemia. Elevated normoxic expression of HIF-1α was observed while downstream hypoxia-responsive genes were downregulated, suggesting adaptation to low-oxygen environments. Naked mole-rat hearts showed reduced succinate build-up during ischemia and negligible tissue damage following ischemia-reperfusion injury. These adaptive evolutionary traits reflect a unique hypoxic and eusocial lifestyle that collectively may contribute to their longevity and health span., Heart transcriptomes from various African mole-rat species and the Hottentot golden mole. Total RNA extraction and analysis was performed commercially by BGI Tech Solutions (Hong Kong)., , # Naked mole rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles

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We performed RNAseq, metabolomics and pathway enrichment analysis on cardiac tissue from naked mole-rats (Heterocephalus glaber) and from seven other members of African mole rat genera, Cape mole-rat (Georychus capensis), Cape dune mole-rat (Bathyergus suillus), Common mole-rat (Cryptomys hottentotus hottentotus), Natal mole-rat (C. h. natalenesis), Mahali mole rat (C. h. mahali), Highveld mole-rat (C. h. pretoriae) and Damaraland mole-rats (Fukomys damarensis) representing differing burrow and soil types, degrees of sociality, lifespan and hypoxia tolerance. In addition, we include the evolutionarily highly divergent hottentot golden mole (Ambysomus hottentotus), an Afrotherian subterranean, solitary mammal, and the C57/BL6 laboratory mouse as a standard mammal control. After RNA sequencing, we removed the reads mapped to rRNAs and get rawdata, then we filtered t...

裸鼹鼠（Heterocephalus glaber）是一类真社会性（eusocial）哺乳动物，兼具超长寿命（可达37年）、卓越的低氧抗性，且无心血管疾病发生。为解析这些极端性状背后的分子机制，本研究对裸鼹鼠心脏组织的代谢组学（metabolomics）与转录组测序（RNAseq）数据，与其他非洲鼹鼠类群进行了对比分析。我们鉴定出裸鼹鼠特有的代谢与遗传适应特征，包括糖原水平升高，这使其可在心脏缺血期间通过糖酵解生成ATP。研究观察到缺氧诱导因子-1α（HIF-1α）的常氧表达水平升高，而其下游的低氧应答基因则表达下调，提示裸鼹鼠已适应低氧环境。裸鼹鼠的心脏在缺血过程中琥珀酸蓄积量更低，且缺血-再灌注损伤（ischemia-reperfusion injury）后几乎无组织损伤。这些适应性进化特征反映了其独特的低氧与真社会性生活方式，或共同促成了其超长寿命与健康寿命。此外，本研究还纳入了多种非洲鼹鼠物种及霍屯督金鼹的心脏转录组。总RNA提取与分析由华大基因科技服务（香港）有限公司（BGI Tech Solutions (Hong Kong)）商业完成。

# 裸鼹鼠具有独特的心脏代谢与遗传适应特征，以适应地下低氧生活环境

我们对裸鼹鼠（Heterocephalus glaber）以及其他7种非洲鼹鼠属物种的心脏组织开展了转录组测序（RNAseq）、代谢组学分析与通路富集分析。这7种非洲鼹鼠分别为：岬鼠（Georychus capensis）、岬沙丘鼹鼠（Bathyergus suillus）、普通鼹鼠（Cryptomys hottentotus hottentotus）、纳塔尔鼹鼠（C. h. natalenesis）、马哈利鼹鼠（C. h. mahali）、高地鼹鼠（C. h. pretoriae）以及达马拉兰鼹鼠（Fukomys damarensis），它们在洞穴类型、土壤特性、社会性行为程度、寿命及低氧耐受能力上均存在差异。此外，本研究还纳入了进化上高度分化的霍屯督金鼹（Ambysomus hottentotus）——一种非洲兽总目地下独居哺乳动物，以及C57/BL6实验室小鼠作为标准哺乳动物对照。完成RNA测序后，我们移除了比对到rRNA的测序reads以获得原始数据，随后对数据进行过滤……