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. 2022 Dec 12;13:7670. doi: 10.1038/s41467-022-35357-4

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© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, 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. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a Regression coefficients for the 75 SOMAmers with age associations verified in healthy volunteers (HV) cerebrospinal fluid (CSF). Blue triangles compare effect sizes (regression coefficients) of physiological age on protein concentrations in serum (external HV cohort from INTERVAL study; x-axis) versus CSF (internal HV cohort; y-axis). Circles correspond to multiple sclerosis (MS) CSF coefficients with concordant (black) or discordant (red) associations with age compared to HV cohorts. Vertical lines connect the CSF coefficients for MS and HV cohorts for the same biomarker. b Example of adjusting measured CSF concentrations of a single protein (growth differentiation factor 15; GDF15) by subtracting effect of healthy aging. GDF15 log-transformed relative fluorescent unit (RFU) values (y-axis) versus age (x-axis) are displayed for HV (top) and MS (bottom) cohorts, before (left) and after (right) adjustment. The HV simple linear regression line (blue) used for the adjustment is superimposed on each panel. The coefficient of determination [R²] and the corresponding p-value were extracted from the linear model (represented by the black line) of HV age-adjusted GDF15 values versus age in MS patients. c Heatmap displaying the standardized expression (log-scaled z-scores) for the 75 selected SOMAmers (rows, for ordered list of proteins, see Supplementary Data 15), separated based on HV/MS concordance or discordance, for all patient samples (columns). Corresponding ages for each participant are displayed in ascending order at the top of the heatmap. d Selected pathways identified using functional enrichment STRING analysis along with Benjamini–Hochberg-adjusted –log10(p-values) describing how significant the functional enrichment is for age concordant and discordant proteins, respectively. See also Supplementary Data 1 and Supplementary Data 2. All statistical tests were two-sided. Source data are provided as a Source Data file.