Vascular aging leading to microvessel depletion is a key element of organismal aging. The proposed mechanism is a deficiency of vascular endothelial growth factor (VEGF) signaling in the endothelial cells (EC), linked to the increase of a receptor in a soluble form (sVEGFR1) preventing VEGF from binding to its active receptor (VEGFR2). Without the VEGF survival signal, ECs may become senescent, contributing to aging and to various pulmonary pathologies. Deficiency of VEGF signaling in EC senescence could represent a determining element of lung aging and diseases such as pulmonary hypertension (PH) and emphysema.