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

dc.contributor.authorFaulkes, Christopher G.
dc.contributor.authorEykyn, Thomas R.
dc.contributor.authorMiljkovic, Jan Lj.
dc.contributor.authorGilbert, James D.
dc.contributor.authorCharles, Rebecca L.
dc.contributor.authorPrag, Hiran A.
dc.contributor.authorPatel, Nikayla
dc.contributor.authorHart, Daniel William
dc.contributor.authorMurphy, Michael P.
dc.contributor.authorBennett, Nigel Charles
dc.contributor.authorAksentijevic, Dunja
dc.date.accessioned2025-02-26T06:05:26Z
dc.date.available2025-02-26T06:05:26Z
dc.date.issued2024-03-27
dc.descriptionDATA AVAILABILITY : The RNAseq data generated in this study have been deposited in the ArrayExpress database under accession code E-MTAB-13808. All data generated in this study have been deposited (open access) in the Dryad database, and can be accessed here: https://doi.org/10.5061/dryad. w9ghx3fts and https://doi.org/10.5061/dryad.66t1g1k66. Source data are provided in this paper.en_US
dc.description.abstractThe 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.en_US
dc.description.departmentMammal Research Instituteen_US
dc.description.departmentZoology and Entomologyen_US
dc.description.librarianam2024en_US
dc.description.sdgSDG-03:Good heatlh and well-beingen_US
dc.description.sponsorshipThe Wellcome Trust Career Re-entry fellowship; supported by: the School of Biological and Behavioural Sciences, Bart’s Charity, BHF MRes studentship, the Medical Research Council, the Medical Research Council UK, a Wellcome Trust Investigator award; SARChI Chair of Mammal Behavioural Ecology and Physiology; Biotechnology and Biological Sciences Research Council BLAST Pump Priming Award; NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and KCL; the Centre of Excellence in Medical Engineering funded by the Wellcome Trust and EPSRC; and the BHF Centre of Research Excellence (RE/18/2/34213).en_US
dc.description.urihttps://www.nature.com/ncomms/en_US
dc.identifier.citationFaulkes, C.G., Eykyn, T.R., Miljkovic, J.Lj. et al. 2024, 'Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles', Nature Communications, vol. 15, art. 2204, pp.1-13. https://DOI.org/10.1038/s41467-024-46470-x.en_US
dc.identifier.issn2041-1723 (online)
dc.identifier.other10.1038/s41467-024-46470-x
dc.identifier.urihttp://hdl.handle.net/2263/101217
dc.language.isoenen_US
dc.publisherNature Researchen_US
dc.rights© The Author(s) 2024. Open access. This article is licensed under a Creative Commons Attribution 4.0 International License.en_US
dc.subjectHeterocephalus glaberen_US
dc.subjectCardiovascular diseaseen_US
dc.subjectHealth spanen_US
dc.subjectCardiac ischemiaen_US
dc.subjectNaked mole-rat (Heterocephalus glaber)en_US
dc.subjectNaked mole-rat (NMR)en_US
dc.subjectSDG-03: Good health and well-beingen_US
dc.titleNaked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestylesen_US
dc.typeArticleen_US

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