Endothelial senescence drives intrinsic skin aging via the neuroimmune CGRP-mast cell axis in mice.

ABSTRACT: Aging is accompanied by progressive vascular dysfunction, but its effects on skin aging remain poorly understood. Although endothelial cell (EC) senescence is implicated in various age-related diseases, its specific role in dermal aging remains unclear. Here we show that EC senescence contributes to intrinsic skin aging through immune dysregulation. Using an EC-specific senescent mouse model, we observe mast cell activation driven by the neuropeptide calcitonin gene-related peptide (CGRP), independent of traditional IgE-mediated pathways. Senescent ECs secreted pro-inflammatory senescence-associated secretory phenotype (SASP) factors, activating dermal neurons to produce CGRP, leading to mast cell degranulation and subsequent skin aging phenotypes. Pharmacological stabilization of mast cel

SUBMITTER: Wicaksono SA 

PROVIDER: S-EPMC12658021 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature