IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-61815-w.html
   My bibliography  Save this article

Activated GDF11/8 subforms predict cardiovascular events and mortality in humans

Author

Listed:
  • Ryan G. Walker

    (Harvard University)

  • Tomohiro Kato

    (Harvard University)

  • Laura Ben Driss

    (Harvard University)

  • Stephen A. Williams

    (SomaLogic Inc
    Standard Biotools Inc)

  • Michael A. Hinterberg

    (SomaLogic Inc)

  • Nebojsa Janjic

    (SomaLogic Inc)

  • Amy D. Gelinas

    (SomaLogic Inc)

  • Meredith A. Carpenter

    (SomaLogic Inc
    Standard Biotools Inc)

  • Chandramohan Kattamuri

    (University of Cincinnati College of Medicine)

  • Joan E. Walter

    (University of Basel)

  • Christian Mueller

    (University of Basel)

  • Kourtney R. Mendello

    (Harvard University)

  • Justis V. Gordon

    (Harvard University)

  • Keenan A. Walker

    (National Institute on Aging)

  • Josef Coresh

    (Johns Hopkins Bloomberg School of Public Health
    Johns Hopkins Bloomberg School of Public Health)

  • Shalender Bhasin

    (Harvard Medical School)

  • Lee L. Rubin

    (Harvard University
    Broad Institute of MIT and Harvard)

  • Amy J. Wagers

    (Harvard University
    Joslin Diabetes Center
    Harvard Medical School)

  • Thomas B. Thompson

    (University of Cincinnati College of Medicine)

  • Peter Ganz

    (University of California)

  • Richard T. Lee

    (Harvard University)

Abstract

Circulating Growth Differentiation Factors 11 and 8 (GDF11/8) exist in both latent and active forms, and it is unclear if specific forms can predict disease outcomes. Our data suggest that a dual-specific aptamer selectively binds GDF11/8 after prodomain activation. In 11,609 patients at risk for future cardiovascular events, low dual-specific aptamer-detected GDF11/8 levels strongly predicted adverse outcomes, including cardiovascular events (HR = 0.43, p = 9.1 × 10⁻⁶³) and all-cause mortality (HR = 0.33, p = 4.8 × 10⁻⁴⁰). Use of selective aptamers suggested that results observed with the dual-specific aptamer for cardiovascular and mortality risk replicated with a GDF8 aptamer although with a smaller effect size. In a second cohort of 4110 individuals (ARIC), low dual-specific aptamer-detected GDF11/8 levels also predicted increased 8 year dementia risk (HR = 0.66, p = 0.00148). Our findings reveal that activation of GDF11/8 may be a factor in future aging-related cardiovascular and cognitive decline.

Suggested Citation

  • Ryan G. Walker & Tomohiro Kato & Laura Ben Driss & Stephen A. Williams & Michael A. Hinterberg & Nebojsa Janjic & Amy D. Gelinas & Meredith A. Carpenter & Chandramohan Kattamuri & Joan E. Walter & Chr, 2025. "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61815-w
    DOI: 10.1038/s41467-025-61815-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-61815-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-61815-w?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
    ---><---

    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:16:y:2025:i:1:d:10.1038_s41467-025-61815-w. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.