PDE1C and aneurysm: Nevertheless, we here observe an effect on senescence markers p16 and p21. In a model of abdominal aorta aneurysm, it was shown that PDE1C knockout attenuated aneurysm formation and lowered VSMC senescence involving p21. Allosteric activation of the senescence-regulating deacetylase Sirtuin-1 by cAMP, which is increased by PDE1 inhibition, was implicated (Zhang et al., 2021).