The autophagy enhancer spermidine reverses arterial aging.
The autophagy enhancer spermidine reverses arterial aging.
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DOI：
10.1016/j.mad.2013.04.004
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发表时间：
2013-07
影响因子：
5.3
通讯作者：
Seals, Douglas R.
中科院分区：
文献类型：
--
作者：
LaRocca, Thomas J.;Gioscia-Ryan, Rachel A.;Hearon, Christopher M., Jr.;Seals, Douglas R.
动脉老化以大弹性动脉硬化和动脉内皮功能障碍为特征，增加了心血管疾病（CVD）的风险。我们测试了一种假设，即亚精胺，一种与抗衰老过程自噬相关的营养物质，可以改善动脉衰老。主动脉脉波速度（aPWV）是衡量动脉硬度的指标，老龄小鼠（0,28个月）比年轻C57BL6小鼠（Y， 4个月，P < 0.05）高20%。动脉内皮依赖性扩张（EDD）是内皮功能的一项指标，由于一氧化氮（NO）的生物利用度降低，O组动脉内皮依赖性扩张（EDD）降低了约25% （P < 0.05 vs. Y）。这些损伤与O动脉氧化应激（硝基酪氨酸）、超氧化物产生和蛋白质交联（晚期糖基化终产物，AGEs）升高有关（均P < 0.05）。补充亚精胺可使aPWV正常化，恢复no介导的EDD，减少o中硝基酪氨酸、超氧化物、AGEs和胶原蛋白。这些作用与增强动脉自噬标志物的表达有关，体外实验表明亚精胺对血管的保护是自噬依赖的。本研究结果表明，亚精胺通过提高NO生物利用度、降低氧化应激、改变结构因子和增强自噬，对动脉具有有效的抗衰老作用。亚精胺可能是一种很有前途的治疗动脉老化和预防与年龄相关的心血管疾病的营养品。
Arterial aging, characterized by stiffening of large elastic arteries and the development of arterial endothelial dysfunction, increases cardiovascular disease (CVD) risk. We tested the hypothesis that spermidine, a nutrient associated with the anti-aging process autophagy, would improve arterial aging. Aortic pulse wave velocity (aPWV), a measure of arterial stiffness, was ~20% greater in old (O, 28 months) compared with young C57BL6 mice (Y, 4 months, P < 0.05). Arterial endothelium-dependent dilation (EDD), a measure of endothelial function, was ~25% lower in O (P < 0.05 vs. Y) due to reduced nitric oxide (NO) bioavailability. These impairments were associated with greater arterial oxidative stress (nitrotyrosine), superoxide production, and protein cross-linking (advanced glycation end-products, AGEs) in O (all P < 0.05). Spermidine supplementation normalized aPWV, restored NO-mediated EDD and reduced nitrotyrosine, superoxide, AGEs and collagen in O. These effects of spermidine were associated with enhanced arterial expression of autophagy markers, and in vitro experiments demonstrated that vascular protection by spermidine was autophagy-dependent. Our results indicate that spermidine exerts a potent anti-aging influence on arteries by increasing NO bioavailability, reducing oxidative stress, modifying structural factors and enhancing autophagy. Spermidine may be a promising nutraceutical treatment for arterial aging and prevention of age-associated CVD.
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影响因子：
37.8
作者：
Mitchell GF;Hwang SJ;Vasan RS;Larson MG;Pencina MJ;Hamburg NM;Vita JA;Levy D;Benjamin EJ
通讯作者：
Benjamin EJ
影响因子：
20.1
作者：
North BJ;Sinclair DA
通讯作者：
Sinclair DA
影响因子：
3.6
作者：
Lydakis, Charalampos;Stefanaki, Evaggelia;Lydaki, Danai
通讯作者：
Lydaki, Danai
影响因子：
7.3
作者：
GRYGLEWSKI, RJ;ZEMBOWICZ, A;VANE, JR
通讯作者：
VANE, JR
DOI：
10.1007/bf01964964
发表时间：
1986-08-01
期刊：
AGENTS AND ACTIONS
影响因子：
--
作者：
KAFY, AML;HAIGH, CG;LEWIS, DA
通讯作者：
LEWIS, DA