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.

Methods
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).