Fig. 6: Comparison of exercise and parabiosis interventions on cell-type-specific aging clocks.

a, Bar plot comparing effects of different interventions. Bar represents the difference (in months) between predicted chronological ages between controls and intervention. Parabiosis cohorts 1 and 2 were averaged. b, Pie charts of the directional effect and overlap of intervention impact on aNSC-NPC chronological aging clock genes (BootstrapCell). Genes are called ‘reversed’ when the sign of the log fold change of gene expression in intervention versus control is opposite to the sign of the coefficient of the gene in the clock (indicated on top of the pie charts). Top GO biological process terms and representative genes are listed underneath. c, Venn diagram representing the overlap of DEGs in aNSC-NPCs between young and old mice (‘age’), old heterochronic mice and old isochronic mice (‘young blood’) and old exercised and old sedentary mice (‘exercise’). Differential expression thresholds required a minimum 1.1-fold expression change with a false discovery rate (FDR) < 0.1. For aging, mice were grouped as either young (<7 months) or old (>20 months). DEGs shared between age and young blood were interferon-stimulated genes. DEGs shared between age and exercise were genes involved in proliferation, metabolism and development. d, Violin and box plots of gene signatures (sum of normalized gene expression for all genes in the gene set) for ‘interferon-γ response’ and ‘negative regulation of neurogenesis’ for aNSC-NPCs in the parabiosis cohort 1 and cohort 2 combined. In the box plot, the line represents the median and the box represents the interquartile range. P values were obtained from the two-sided Wilcoxon rank-sum test (n = 668, 149 and 146 cells for ‘young isochronic’, ‘old isochronic’ and ‘old heterochronic’, respectively). e, As in d but for aNSC-NPCs in the exercise cohort (n = 2,243, 503 and 1,170 cells for ‘young sedentary’, ‘old sedentary’ and ‘old exercise’, respectively).