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

Chris G. Faulkes, Thomas R. Eykyn, Jan Lj. Miljkovic, James D. Gilbert, Rebecca L. Charles, Hiran A. Prag, Nikayla Patel, Daniel W. Hart, Michael P. Murphy, Nigel C. Bennett and Dunja Aksentijevic ()
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Chris G. Faulkes: Queen Mary University of London
Thomas R. Eykyn: School of Biomedical Engineering and Imaging Sciences, King’s College London, St Thomas’ Hospital
Jan Lj. Miljkovic: University of Cambridge, Keith Peters Building
James D. Gilbert: Queen Mary University of London
Rebecca L. Charles: Queen Mary University of London
Hiran A. Prag: University of Cambridge, Keith Peters Building
Nikayla Patel: Queen Mary University of London
Daniel W. Hart: University of Pretoria
Michael P. Murphy: University of Cambridge, Keith Peters Building
Nigel C. Bennett: University of Pretoria
Dunja Aksentijevic: Queen Mary University of London

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract 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 was compared to other African mole-rat genera (Cape, Cape dune, Common, Natal, Mahali, Highveld and Damaraland mole-rats) and evolutionarily divergent mammals (Hottentot golden mole and C57/BL6 mouse). We identify 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 is observed while downstream hypoxia responsive-genes are down-regulated, suggesting adaptation to low oxygen environments. Naked mole-rat hearts show reduced succinate levels during ischemia compared to C57/BL6 mouse and negligible tissue damage following ischemia-reperfusion injury. These evolutionary traits reflect adaptation to a unique hypoxic and eusocial lifestyle that collectively may contribute to their longevity and health span.

Date: 2024
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DOI: 10.1038/s41467-024-46470-x

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