Fig. 10: Higher brain biological age in chronic active multiple sclerosis by both transcriptome and MRI. | Nature Communications

Fig. 10: Higher brain biological age in chronic active multiple sclerosis by both transcriptome and MRI.

From: Spatially-restricted inflammation-induced senescent-like glia in multiple sclerosis and patient-derived organoids

Fig. 10

a Graphical representation of the estimation of the brain biological age by transcriptome or MRI. After obtaining a normative time series for each modality, human brain MS samples or MRI scans were staged for biological vs. chronological age. See “Methods” for additional detail. Created in BioRender. Absinta, M. (2025) https://BioRender.com/d0hxq2g. b Representative 3T MRI case of a man in his ‘50 with MS. Several chronic active lesions (box and magnification) can be seen by MRI as T2-FLAIR-positive hyperintense lesions with a paramagnetic rim (PRL) on susceptibility-based MRI sequences. Scale bars: 10 mm. c Bar plot showing the brain age gap (mean ± SD, years) by transcriptome in brain samples from non-neurological controls (n = 21 samples) and MS (n = 44 samples at different pathological stage). Among all conditions, chronic active lesion edge and core showed higher brain biological age (ANOVA Kruskal–Wallis p < 0.0001, Dunn’s multiple comparison ** p < 0.01, **** p < 0.0001). d Bar plot showing the brain age gap (mean ± SD, years) by MRI analysis in non-neurological controls (n = 22), MS-mimics (n = 44), and MS patients (n = 466). Higher brain age gap is seen in MS patients, especially in those with more than 3 chronic active lesions by MRI (PRL, one-way ANOVA p < 0.0001, Tukey’s post-hoc multiple comparisons * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001). e Scatter plot of chronological vs. brain age (years), by MRI, for each individual (n = 532). One dot equals one individual. MS patients were classified based on the PRL number and color-coded. Brain-age trajectories confirmed prior data as seen in (c). f Reverse Kaplan–Meier curves of the probability of the disability milestone EDSS of ≥4 for both chronological (top, comparison of survival curves using log-rank Mantel–Cox test p = 0.0028, median survival 63 years-old for PRL 0, 61 years-old for PRL 1–3, 58 years-old for PRL > 4, respectively) and biological MRI-brain age (bottom, comparison of survival curves using log-rank Mantel–Cox test p = 0.5 n.s., median survival 73.3 years-old for PRL 0, 71.5 years-old for PRL 1–3, 73.7 years-old for PRL > 4, respectively). snRNA-seq single-nucleus RNA sequencing, MS multiple sclerosis, NAWM normal appearing white matter, PRL paramagnetic rim lesions, EDSS Expanded Disability Status Scale.

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