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

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^*

^*Corresponding author for this work

Imaging Chemistry & Biology

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

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.

Original language	English
Article number	2204
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-46470-x
Publication status	Published - 27 Mar 2024

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Faulkes, C. G., Eykyn, T. R., Miljkovic, J. L., Gilbert, J. D., Charles, R. L., Prag, H. A., Patel, N., Hart, D. W., Murphy, M. P., Bennett, N. C., & Aksentijevic, D. (2024). Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles. Nature Communications, 15(1), Article 2204. https://doi.org/10.1038/s41467-024-46470-x

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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.",

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AU - Charles, Rebecca L.

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AU - Bennett, Nigel C.

AU - Aksentijevic, Dunja

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

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