IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36483-3.html
   My bibliography  Save this article

Methionine adenosyltransferase2A inhibition restores metabolism to improve regenerative capacity and strength of aged skeletal muscle

Author

Listed:
  • Nika Rajabian

    (University at Buffalo, The State University of New York)

  • Izuagie Ikhapoh

    (University at Buffalo, The State University of New York)

  • Shahryar Shahini

    (University at Buffalo, The State University of New York)

  • Debanik Choudhury

    (University at Buffalo, The State University of New York)

  • Ramkumar Thiyagarajan

    (University at Buffalo and Research Service, Veterans Affairs Western New York Healthcare System)

  • Aref Shahini

    (University at Buffalo, The State University of New York)

  • Joseph Kulczyk

    (University at Buffalo, The State University of New York)

  • Kendall Breed

    (University at Buffalo, The State University of New York)

  • Shilpashree Saha

    (University at Buffalo)

  • Mohamed Alaa Mohamed

    (University at Buffalo, The State University of New York)

  • Susan B. Udin

    (University at Buffalo)

  • Aimee Stablewski

    (Roswell Park Comprehensive Cancer Institute)

  • Kenneth Seldeen

    (University at Buffalo and Research Service, Veterans Affairs Western New York Healthcare System)

  • Bruce R. Troen

    (University at Buffalo and Research Service, Veterans Affairs Western New York Healthcare System)

  • Kirkwood Personius

    (University at Buffalo)

  • Stelios T. Andreadis

    (University at Buffalo, The State University of New York
    University at Buffalo
    Center of Excellence in Bioinformatics and Life Sciences
    University at Buffalo)

Abstract

We investigate the age-related metabolic changes that occur in aged and rejuvenated myoblasts using in vitro and in vivo models of aging. Metabolic and signaling experiments reveal that human senescent myoblasts and myoblasts from a mouse model of premature aging suffer from impaired glycolysis, insulin resistance, and generate Adenosine triphosphate by catabolizing methionine via a methionine adenosyl-transferase 2A-dependant mechanism, producing significant levels of ammonium that may further contribute to cellular senescence. Expression of the pluripotency factor NANOG downregulates methionine adenosyltransferase 2 A, decreases ammonium, restores insulin sensitivity, increases glucose uptake, and enhances muscle regeneration post-injury. Similarly, selective inhibition of methionine adenosyltransferase 2 A activates Akt2 signaling, repairs pyruvate kinase, restores glycolysis, and enhances regeneration, which leads to significant enhancement of muscle strength in a mouse model of premature aging. Collectively, our investigation indicates that inhibiting methionine metabolism may restore age-associated impairments with significant gain in muscle function.

Suggested Citation

  • Nika Rajabian & Izuagie Ikhapoh & Shahryar Shahini & Debanik Choudhury & Ramkumar Thiyagarajan & Aref Shahini & Joseph Kulczyk & Kendall Breed & Shilpashree Saha & Mohamed Alaa Mohamed & Susan B. Udin, 2023. "Methionine adenosyltransferase2A inhibition restores metabolism to improve regenerative capacity and strength of aged skeletal muscle," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36483-3
    DOI: 10.1038/s41467-023-36483-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36483-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-36483-3?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. Daniela Piazzolla & Adelaida R. Palla & Cristina Pantoja & Marta Cañamero & Ignacio Perez de Castro & Sagrario Ortega & Gonzalo Gómez-López & Orlando Dominguez & Diego Megías & Giovanna Roncador & Jos, 2014. "Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia," Nature Communications, Nature, vol. 5(1), pages 1-14, September.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Pihu Mehrotra & James Jablonski & John Toftegaard & Yali Zhang & Shahryar Shahini & Jianmin Wang & Carey W. Hung & Reilly Ellis & Gabriella Kayal & Nika Rajabian & Song Liu & Kelly C. S. Roballo & Sus, 2024. "Skeletal muscle reprogramming enhances reinnervation after peripheral nerve injury," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    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. Naveen Kumar & Pon Ganish Prakash & Christian Wentland & Shilpa Mary Kurian & Gaurav Jethva & Volker Brinkmann & Hans-Joachim Mollenkopf & Tobias Krammer & Christophe Toussaint & Antoine-Emmanuel Sali, 2024. "Decoding spatiotemporal transcriptional dynamics and epithelial fibroblast crosstalk during gastroesophageal junction development through single cell analysis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Pihu Mehrotra & James Jablonski & John Toftegaard & Yali Zhang & Shahryar Shahini & Jianmin Wang & Carey W. Hung & Reilly Ellis & Gabriella Kayal & Nika Rajabian & Song Liu & Kelly C. S. Roballo & Sus, 2024. "Skeletal muscle reprogramming enhances reinnervation after peripheral nerve injury," Nature Communications, Nature, vol. 15(1), pages 1-19, 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:14:y:2023:i:1:d:10.1038_s41467-023-36483-3. 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.