Figure 3. Heatmap of associations between mortality-associated plasma proteins and biological aging measures. (IMAGE)

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Figure 3. Heatmap of associations between mortality-associated plasma proteins and biological aging measures.

Caption

Values represent standardized regression coefficients (β). Red indicates positive associations (accelerated aging) and blue indicates negative associations (younger biological age). * indicates that the association with the corresponding biological aging measure was not statistically significant (p ≥ 0.05). All other associations were statistically significant. Brain and Immune aging measures show particularly strong cross-cohort agreement, especially for HE4, MIC-1, ERBB1, NOTUM, and IGFBP-2. We observed distinct organ-specific patterns, validating the biological specificity of the aging measures. N-terminal pro-BNP, a well-established cardiac marker, demonstrated the strongest association specifically with heart aging in both LonGenity (β = 1.34, p < 2.1E-100) and BLSA (β = 0.94, p < 2E-16) cohorts, while showing non-significant or weaker associations with kidney aging in these models. ERBB1: epidermal growth factor receptor; ANTXR2: anthrax toxin receptor 2; IDS: iduronate 2-sulfatase; IGFBP-2: insulin-like growth factor-binding protein 2; MIC-1: macrophage inhibitory cytokine 1; GDF-11/8: growth differentiation factor-11/8; HYAL1: hyaluronidase-1; HE4: human epididymis protein 4; C1QT3: C1q and tumor necrosis factor-related protein 3; TSP2: thrombospondin-2; SVEP1: sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1.

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© Sanish Sathyan, Nir Barzilai, et al., 2027. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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