Naked mole rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles (non-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 down-regulated, 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., Langendorff Heart Perfusion
Beating hearts were excised from terminally anaesthetized naked mole rats (n=5) and C57/BL6 mice (n=5) (Charles River, UK) for Langendorff perfusions. After 20 minutes of equilibration, hearts were subject to 20 minutes of global normothermic ischemia. Hearts were snap frozen at the end of the protocol using a Wollenberger clamp pre-cooled in liquid N2. Ischemia/reperfusion (I/R) outcome in NMRs was compared to C57BL6 mouse heart due to their anatomical, physiological, and genetic similarity to humans. We were unable to repeat ex vivo cardiac perfusion protocols in all other 5 mole rat genera hearts as they are not kept in captive colonies in the UK. Myocardial infarct size quantification Myocardial infarct size was quantified. In brief, after 20 min of equilibration, Langendorff perfused hearts (n=3/ group) were subject to 20 of global normothermic ischemia and 2 hours of reperfusion. At the end of the protocol, hearts were perfused for 10 mins with 3% triph..., , # Naked mole rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles (non-genetic data)

Experiments were carried out on heart tissue collected from naked mole rat (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. Tissue was also collected from C57/Bl6 mouse heart. We carried out the study to understand what adaptation exist in the hearts of naked mole rats versus all the others so they are resistant to heart disease including heart attacks.

### Description of the Data and file structure

Raw data is provided in an Excel table: 1H NMR...