Angiogenesis (VEGF)

Angiogenesis is the growth of new blood vessels from existing capillaries. The main driver is VEGF-A (vascular endothelial growth factor-A), a protein that binds two receptors (VEGFR-1 and VEGFR-2) on the cells lining vessels, triggering them to multiply, migrate, and form tubes. VEGF gets switched on by low oxygen (via HIF-1α), by the shear stress of blood flow, and by the coactivator PGC-1α. Together these match your capillary supply to metabolic demand. With age, your skeletal muscle loses capillaries (a process called rarefaction). Resting VEGF protein runs about 35% lower, and the exercise-induced rise in VEGF mRNA is roughly 50% blunted in aged versus young women (Croley et al. 2005), with similar findings in men; the capillary-to-fiber ratio drops about 25% in older sedentary people (Zmudzka et al. 2022). The good news: regular aerobic training partly reverses this. It can raise capillary density by up to about 28%, and the capillary-to-fiber ratio by up to about 43%, even in older adults, through local low-oxygen signals, nitric oxide, and PGC-1α-driven VEGF. Drug-based VEGF delivery is still experimental, with mixed results in peripheral artery disease trials. So exercise is the only established way to restore age-related capillary loss.

Last reviewed: June 22, 2026

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