The Influence of Age on Notch1 and VEGF-A Responses During Exercise

Notch1 and vascular endothelial growth factor-A (VEGF-A) are polyfunctional signaling molecules that can be activated in response to elevated shear stress. In nonpathological conditions, they are integral to healthy endothelium; however, it is unknown whether their responsiveness during aerobic exercise, a robust shear stimulus, is impacted by age. Accordingly, in this exploratory cross-sectional study, concentrations of VEGF-A and Notch1 extracellular domain (NECD) were quantified in twenty-nine (13 females) healthy adults (mean age: 32 years, range: 20-65), using venous blood samples taken at rest, immediately postexercise (cycle V̇O₂ peak test), and following 15 min of recovery. NECD concentrations remained stable across exercise (condition effect: p = 0.186); however, overall NECD was elevated with age (age effect: p = 0.024). Moreover, the change in NECD following exercise varied by age (age × condition interaction: p = 0.028) and was significantly associated with carotid intima-media thickness (cIMT) (p = 0.005, r = 0.475). Conversely, no significant main effects were found for VEGF-A (all p > 0.05), and VEGF-A was not associated with cIMT (p = 0.283, ρ = -0.114). These results indicate that the Notch1, but not VEGF-A, response to acute exercise is altered across adult aging, with cIMT showing a secondary association that potentially reflects underlying vascular structural influences.