The development of long-lasting antihypertensive therapies represents a crucial unmet need. Hilgers et al. now report that mice overexpressing the redox protein thioredoxin (TRX) are protected from age-related hypertension. Furthermore, injection of aged mice with recombinant human TRX (rhTRX) lowered blood pressure to levels seen in young mice, which were maintained for at least 20 days. RhTRX injection or TRX overexpression in mice also decreased arterial stiffness, attenuated endothelial dysfunction, increased nitric oxide production and reduced superoxide anion release.