Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles
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| dc.contributor.author | Faulkes, Christopher G.
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| dc.contributor.author | Eykyn, Thomas R.
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| dc.contributor.author | Miljkovic, Jan Lj.
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| dc.contributor.author | Gilbert, James D.
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| dc.contributor.author | Charles, Rebecca L.
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| dc.contributor.author | Prag, Hiran A.
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| dc.contributor.author | Patel, Nikayla
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| dc.contributor.author | Hart, Daniel William
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| dc.contributor.author | Murphy, Michael P.
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| dc.contributor.author | Bennett, Nigel Charles
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| dc.contributor.author | Aksentijevic, Dunja
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| dc.date.accessioned | 2025-02-26T06:05:26Z | |
| dc.date.available | 2025-02-26T06:05:26Z | |
| dc.date.issued | 2024-03-27 | |
| dc.description | DATA 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.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. | en_US |
| dc.description.department | Mammal Research Institute | en_US |
| dc.description.department | Zoology and Entomology | en_US |
| dc.description.librarian | am2024 | en_US |
| dc.description.sdg | SDG-03:Good heatlh and well-being | en_US |
| dc.description.sponsorship | The 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.uri | https://www.nature.com/ncomms/ | en_US |
| dc.identifier.citation | Faulkes, 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.issn | 2041-1723 (online) | |
| dc.identifier.other | 10.1038/s41467-024-46470-x | |
| dc.identifier.uri | http://hdl.handle.net/2263/101217 | |
| dc.language.iso | en | en_US |
| dc.publisher | Nature Research | en_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.subject | Heterocephalus glaber | en_US |
| dc.subject | Cardiovascular disease | en_US |
| dc.subject | Health span | en_US |
| dc.subject | Cardiac ischemia | en_US |
| dc.subject | Naked mole-rat (Heterocephalus glaber) | en_US |
| dc.subject | Naked mole-rat (NMR) | en_US |
| dc.subject | SDG-03: Good health and well-being | en_US |
| dc.title | Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles | en_US |
| dc.type | Article | en_US |
