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

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, Christian Mueller, Kourtney R. Mendello, Justis V. Gordon, Keenan A. Walker, Josef Coresh, Shalender Bhasin, Lee L. Rubin, Amy J. Wagers, Thomas B. Thompson, Peter Ganz () and Richard T. Lee ()
Additional contact information
Ryan G. Walker: Harvard University
Tomohiro Kato: Harvard University
Laura Ben Driss: Harvard University
Stephen A. Williams: SomaLogic Inc
Michael A. Hinterberg: SomaLogic Inc
Nebojsa Janjic: SomaLogic Inc
Amy D. Gelinas: SomaLogic Inc
Meredith A. Carpenter: SomaLogic 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
Shalender Bhasin: Harvard Medical School
Lee L. Rubin: Harvard University
Amy J. Wagers: Harvard University
Thomas B. Thompson: University of Cincinnati College of Medicine
Peter Ganz: University of California
Richard T. Lee: Harvard University

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-61815-w

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