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; Dunja Aksentijevic

doi:10.1038/s41467-024-46470-x

Nature Communications (Mar 2024)

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,
Dunja Aksentijevic

Affiliations

Chris G. Faulkes: School of Biological and Behavioural Sciences, Fogg Building, Mile End Road, Queen Mary University of London
Thomas R. Eykyn: Department of Imaging Chemistry and Biology, School of Biomedical Engineering and Imaging Sciences, King’s College London, St Thomas’ Hospital
Jan Lj. Miljkovic: MRC Mitochondrial Biology Unit, University of Cambridge, Keith Peters Building
James D. Gilbert: School of Biological and Behavioural Sciences, Fogg Building, Mile End Road, Queen Mary University of London
Rebecca L. Charles: Centre for Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Bart’s and the London Faculty of Medicine and Dentistry, Queen Mary University of London
Hiran A. Prag: MRC Mitochondrial Biology Unit, University of Cambridge, Keith Peters Building
Nikayla Patel: Centre for Biochemical Pharmacology, William Harvey Research Institute, Bart’s and the London Faculty of Medicine and Dentistry, Queen Mary University of London
Daniel W. Hart: Department of Zoology and Entomology, Mammal Research Institute, University of Pretoria
Michael P. Murphy: MRC Mitochondrial Biology Unit, University of Cambridge, Keith Peters Building
Nigel C. Bennett: Department of Zoology and Entomology, Mammal Research Institute, University of Pretoria
Dunja Aksentijevic: Centre for Biochemical Pharmacology, William Harvey Research Institute, Bart’s and the London Faculty of Medicine and Dentistry, Queen Mary University of London

DOI: https://doi.org/10.1038/s41467-024-46470-x
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 13

Abstract

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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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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