Smith A R, Hagen T M
Department of Biochemistry and Biophysics and Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331, U.S.A.
Biochem Soc Trans. 2003 Dec;31(Pt 6):1447-9. doi: 10.1042/bst0311447.
Aging is the single largest risk factor for cardiovascular diseases, which in turn are the leading cause of death of individuals over the age of 65 years. In part, this risk is due to a profound loss of vasomotor function of the major conduit arteries, primarily because of lower levels of endothelial-derived nitric oxide. The mechanisms involved in vascular dysfunction are not entirely understood, but age-related alterations in eNOS (endothelial nitric oxide synthase) activity appear to be a likely source of the aging lesion. However, age-related changes in cell signalling that ultimately affect eNOS phosphorylation and its activity have not been explored. Results in our laboratory indicate that levels of eNOS phosphorylation in aortas from aged F344xBN rats (28-30 months old) are almost 50% lower than in aortas from young animals (3 months old). Lower eNOS phosphorylation is directly attributable to loss of constitutive Akt/protein kinase B activity. The decline in eNOS phosphorylation can be partially restored by treating old rats with (R)-alpha-lipoic acid. These results thus suggest that age-related changes in eNOS phosphorylation may be a significant factor in the overall loss of vasomotor function in the elderly.
衰老 是心血管疾病的最大单一风险因素，而心血管疾病又是65岁以上人群的主要死因。这种风险部分归因于主要输送动脉血管舒缩功能的严重丧失，主要原因是内皮源性一氧化氮水平降低。血管功能障碍所涉及的机制尚未完全明确，但内皮型一氧化氮合酶（eNOS）活性的年龄相关变化似乎是衰老病变的一个可能来源。然而，最终影响eNOS磷酸化及其活性的细胞信号传导的年龄相关变化尚未得到研究。我们实验室的结果表明，老年F344xBN大鼠（28 - 30个月大）主动脉中eNOS磷酸化水平比幼年动物（3个月大）主动脉中的低近50%。eNOS磷酸化水平降低直接归因于组成型Akt/蛋白激酶B活性的丧失。用（R）-α-硫辛酸治疗老年大鼠可部分恢复eNOS磷酸化水平的下降。因此，这些结果表明，eNOS磷酸化的年龄相关变化可能是老年人血管舒缩功能整体丧失的一个重要因素。
