Habitual aerobic exercise reverses age‐associated increases in transforming growth factor beta 1 in carotid arteries of mice

Aging increases carotid artery stiffness and adventitial collagen in mice. These events are reversed by voluntary wheel running (VR). Transforming growth factor β1 (TGF‐β1) modulates extracellular matrix proteins with aging, but the effect of habitual exercise on TGF‐β1 expression in large elastic arteries is unknown. Carotid artery stiffness was greater in old (O, 31 mo, n=4) vs. young (Y, 7 mo, n=4) adult cage‐control B6D2F1 mice (8.53 ± 2.00 vs. 3.015 ± 1.19 AU, p < 0.05), but not in O (n=4) given access to running wheels (mean distance = 1 km/d) for 12 weeks (3.61 ± 0.83 AU, p < 0.05). Immunohistochemical analysis of carotid arteries from Y (n=6) and O (n=8) cage control mice revealed increases in adventitial TGF‐β1 with aging (5.7E‐05 ± 5.9E‐06 vs. 3.6E‐05 ± 3.5E‐06 AU, P < 0.05), which were reversed by VR in O (n=4) (3.6E‐05 ± 4.2E‐06 AU). In a primary culture of adventitial fibroblasts obtained from Y adult (6 mo) Sprague‐Dawley rats, 24‐hr treatment with TGF‐β1 increased type I collagen (1.38 ± 0.07 vs. 1.0 ± 0.08, P < 0.05, western blot) and superoxide (O 2 − ) production (4514 ± 317 vs. 2828 ± 185, P < 0.05, electron paramagnetic resonance). These preliminary data are consistent with the working hypothesis that habitual aerobic exercise may reverse large elastic artery stiffening with aging in part by reducing O 2 − production, which inhibits adventitial TGF‐β1‐induced adventitial collagen accumulation.