IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46470-x.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    University of Cambridge, Cambridge Biomedical Campus)

  • 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)

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.

Suggested Citation

  • 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 Aksentije, 2024. "Naked mole-rats have distinctive cardiometabolic and genetic adaptations to their underground low-oxygen lifestyles," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46470-x
    DOI: 10.1038/s41467-024-46470-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46470-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-46470-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Eun Bae Kim & Xiaodong Fang & Alexey A. Fushan & Zhiyong Huang & Alexei V. Lobanov & Lijuan Han & Stefano M. Marino & Xiaoqing Sun & Anton A. Turanov & Pengcheng Yang & Sun Hee Yim & Xiang Zhao & Mari, 2011. "Genome sequencing reveals insights into physiology and longevity of the naked mole rat," Nature, Nature, vol. 479(7372), pages 223-227, November.
    2. Dunja Aksentijević & Anja Karlstaedt & Marina V. Basalay & Brett A. O’Brien & David Sanchez-Tatay & Seda Eminaga & Alpesh Thakker & Daniel A. Tennant & William Fuller & Thomas R. Eykyn & Heinrich Taeg, 2020. "Intracellular sodium elevation reprograms cardiac metabolism," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    3. Edward T. Chouchani & Victoria R. Pell & Edoardo Gaude & Dunja Aksentijević & Stephanie Y. Sundier & Ellen L. Robb & Angela Logan & Sergiy M. Nadtochiy & Emily N. J. Ord & Anthony C. Smith & Filmon Ey, 2014. "Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS," Nature, Nature, vol. 515(7527), pages 431-435, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yu Jin Chung & Zoe Hoare & Friedrich Baark & Chak Shun Yu & Jia Guo & William Fuller & Richard Southworth & Doerthe M. Katschinski & Michael P. Murphy & Thomas R. Eykyn & Michael J. Shattock, 2024. "Elevated Na is a dynamic and reversible modulator of mitochondrial metabolism in the heart," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Maithily S. Nanadikar & Ana M. Vergel Leon & Jia Guo & Gijsbert J. Belle & Aline Jatho & Elvina S. Philip & Astrid F. Brandner & Rainer A. Böckmann & Runzhu Shi & Anke Zieseniss & Carla M. Siemssen & , 2023. "IDH3γ functions as a redox switch regulating mitochondrial energy metabolism and contractility in the heart," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Joy Edwards-Hicks & Huizhong Su & Maurizio Mangolini & Kubra K. Yoneten & Jimi Wills & Giovanny Rodriguez-Blanco & Christine Young & Kevin Cho & Heather Barker & Morwenna Muir & Ania Naila Guerrieri &, 2022. "MYC sensitises cells to apoptosis by driving energetic demand," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Jiayi Wang & Mengke Zhao & Meina Wang & Dong Fu & Lin Kang & Yu Xu & Liming Shen & Shilin Jin & Liang Wang & Jing Liu, 2024. "Human neural stem cell-derived artificial organelles to improve oxidative phosphorylation," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    5. Xiaoduo Tang & Jingyan Ren & Xin Wei & Tao Wang & Haiqiu Li & Yihan Sun & Yang Liu & Mingli Chi & Shoujun Zhu & Laijin Lu & Junhu Zhang & Bai Yang, 2023. "Exploiting synergistic effect of CO/NO gases for soft tissue transplantation using a hydrogel patch," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Masataka Kawamura & Catherine Parmentier & Samrat Ray & Sergi Clotet-Freixas & Sharon Leung & Rohan John & Laura Mazilescu & Emmanuel Nogueira & Yuki Noguchi & Toru Goto & Bhranavi Arulratnam & Sujani, 2024. "Normothermic ex vivo kidney perfusion preserves mitochondrial and graft function after warm ischemia and is further enhanced by AP39," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Xueqiang Wang & Xing Zhang & Ke Cao & Mengqi Zeng & Xuyang Fu & Adi Zheng & Feng Zhang & Feng Gao & Xuan Zou & Hao Li & Min Li & Weiqiang Lv & Jie Xu & Jiangang Long & Weijin Zang & Jinghai Chen & Fen, 2022. "Cardiac disruption of SDHAF4-mediated mitochondrial complex II assembly promotes dilated cardiomyopathy," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    8. Pankaj Sharma & Elena Maklashina & Markus Voehler & Sona Balintova & Sarka Dvorakova & Michal Kraus & Katerina Hadrava Vanova & Zuzana Nahacka & Renata Zobalova & Stepana Boukalova & Kristyna Cunatova, 2024. "Disordered-to-ordered transitions in assembly factors allow the complex II catalytic subunit to switch binding partners," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. John O. Onukwufor & M. Arsalan Farooqi & Anežka Vodičková & Shon A. Koren & Aksana Baldzizhar & Brandon J. Berry & Gisela Beutner & George A. Porter & Vsevolod Belousov & Alan Grossfield & Andrew P. W, 2022. "A reversible mitochondrial complex I thiol switch mediates hypoxic avoidance behavior in C. elegans," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    10. Thomas Agius & Raffaella Emsley & Arnaud Lyon & Michael R. MacArthur & Kevin Kiesworo & Anna Faivre & Louis Stavart & Martine Lambelet & David Legouis & Sophie Seigneux & Déla Golshayan & Francois Laz, 2024. "Short-term hypercaloric carbohydrate loading increases surgical stress resilience by inducing FGF21," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46470-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.