Aging induces vascular niche remodeling such as reduction of α-smooth muscle actin+ (α-SMA+) or NG2+ arterioles,138 but increased stromal populations.71 Moreover, nestin+ cells have enriched β3-adrenergic receptors of which stimulation reduces the retention signal CXCR12 resulting in HSC mobilization123 with circadian rhythm.139 This pathway is inhibited in mouse models of type 1 and type 2 diabetes (streptozotocin-induced and db/db mice, respectively).140 Exercise-increased HSPC quiescence is mediated by the reduction of leptin signaling on stromal cells.141. Here, NES is linked to type 2 diabetes mellitus.