Fig. 5.
Presence of old blood in young mice mimics age-related changes in vascular expression of genes associated with the pathogenesis of aorta aneurysms Panel A: Gene set enrichment analysis (GSEA) to test the effect of aging on the enrichment of the set of genes associated with the pathogenesis of aorta aneurysms by comparing aorta samples derived from isochronic parabiont young mice [parabiont: young; Y–(Y)] and isochronic parabiont aged mice [parabiont: aged; A–(A)]. Aging-induced gene expression changes were ranked from most up-regulated (left) to most down-regulated (right). Ticks represent genes encoding aneurysm-related factors. Shown is a running-sum statistic (enrichment score) based on panel D, increasing when a gene is a member of the aneurysm-related gene set and decreasing when it is not. Panel B: GSEA showing the effect of exposure to old blood on the enrichment of aneurysm-related genes. Aorta samples derived from isochronic parabiont young mice [parabiont: young; Y–(Y)] and heterochronic parabiont young mice [parabiont: aged; Y–(A)] were compared. Note that in aged mice, enrichment scores increased predominantly on the right indicating age-related down-regulation of genes related to extracellular matrix homeostasis. In response to the presence of old blood in young mice, enrichment scores showed similar increases on the right, indicating that the presence of old blood in young mice mimics the effects of aging on aneurysm-related genes. Panel C: Youngblood had no consistent effect on aneurysm-related genes (comparison: A–(Y) vs. A–(A)). Panel D: The heat maps are graphical representations of normalized expression values of aneurysm-related genes. Hierarchical clustering analysis revealed the similarities on aortic expression profiles of aneurysm-related genes in aged mice and old blood exposed young mice. Panel E: Old blood-induced changes in aneurysm-related gene expression (log2 fold changes; Y–(A) vs. Y–(Y)) plotted against age-related changes (log2 fold changes; A–(A) vs. Y–(Y)) in aneurysm-related gene expression. Note that many aneurysm-related genes are dysregulated both in aging and by the presence of old blood in young animals as well