Figure 1. Damaged nuclear DNA export, sensing and clearance in aging-related inflammation. Left, schematic showing nuclear-autophagy-lysosome DNA clearance pathway in which nuclear DNA trafficked to cytosol is enclosed by autophagosomes and delivered to lysosomes for degradation by DNASE2A. Excess extranuclear DNA accumulated upon increased DNA damage (old cells), deficit repair (AT), deformed nuclear barrier (HGPS), or defective degradation (Dnase2a-/-), can activate innate DNA sensing cGAS-cGAMP-STING pathway and induce aging-associated IFN response and inflammation. Right, immunofluorescent images of anti-dsDNA staining (green) in replicative senescent (SEN), AT and HGPS human fibroblasts. Pseudo-colored (red) overlaid to enhance visualization of lobulated nuclear envelop and excess extranuclear DNA burden in forms of buds, speckles and large aggregates (asterisk in AT); N, nucleus.