Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA.
Nutrients. 2023 May 26;15(11):2490. doi: 10.3390/nu15112490.
Nitric oxide (NO) (co)regulates many physiological processes in the body. Its short-lived free radicals force synthesis in situ and on-demand, without storage possibility. Local oxygen availability determines the origin of NO-either by synthesis by nitric oxide synthases (NOS) or by the reduction of nitrate to nitrite to NO by nitrate/nitrite reductases. The existence of nitrate reservoirs, mainly in skeletal muscle, assures the local and systemic availability of NO. Aging is accompanied by changes in metabolic pathways, leading to a decrease in NO availability. We explored age-related changes in various rat organs and tissues. We found differences in nitrate and nitrite contents in tissues of old and young rats at baseline levels, with nitrate levels being generally higher and nitrite levels being generally lower in old rats. However, there were no differences in the levels of nitrate-transporting proteins and nitrate reductase between old and young rats, with the exception of in the eye. Increased dietary nitrate led to significantly higher nitrate enrichment in the majority of old rat organs compared to young rats, suggesting that the nitrate reduction pathway is not affected by aging. We hypothesize that age-related NO accessibility changes originate either from the NOS pathway or from changes in NO downstream signaling (sGC/PDE5). Both possibilities need further investigation.
一氧化氮 (NO) (共同) 调节体内许多生理过程。其短寿命自由基迫使原位和按需合成,没有存储的可能性。局部氧可用性决定了 NO 的来源——要么通过一氧化氮合酶 (NOS) 合成,要么通过硝酸盐/亚硝酸盐还原酶将硝酸盐还原为亚硝酸盐再转化为 NO。硝酸盐储存库的存在(主要在骨骼肌中)保证了 NO 的局部和全身可用性。衰老伴随着代谢途径的变化,导致 NO 的可用性降低。我们探索了不同大鼠器官和组织的与年龄相关的变化。我们发现,在基线水平下,老年和年轻大鼠组织中的硝酸盐和亚硝酸盐含量存在差异,老年大鼠的硝酸盐水平普遍较高,亚硝酸盐水平普遍较低。然而,除了眼睛之外,在年轻大鼠和老年大鼠之间,硝酸盐转运蛋白和硝酸盐还原酶的水平没有差异。增加膳食硝酸盐会导致大多数老年大鼠器官中的硝酸盐富集显著增加,与年轻大鼠相比,这表明硝酸盐还原途径不受衰老的影响。我们假设与年龄相关的 NO 可及性变化要么源于 NOS 途径,要么源于 NO 下游信号(sGC/PDE5)的变化。这两种可能性都需要进一步研究。