Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Geriatr Gerontol Int. 2013 Apr;13(2):490-6. doi: 10.1111/j.1447-0594.2012.00929.x. Epub 2012 Aug 31.
Catecholamines, which are physiologically important neurotransmitters and hormones, apparently decrease in the brain and plasma as some species age. Because this observation has engendered controversy, we used mice to investigate whether age-related changes occur in adrenal catecholamine levels and in the expression of catecholamine synthetic enzymes.
Adrenal glands were collected from male C57BL/6NCr mice at the ages of 6, 12 and 24 months. Catecholamines, such as dopamine (DA), noradrenaline (NA) and adrenaline (AD) from those glands, were measured by using a highly sensitive liquid chromatographic method with peroxyoxalate chemiluminescence reaction detection. Tyrosine hydroxylase (TH), dopa decarboxylase, dopamine beta hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) mRNA expression levels were measured by quantitative real-time polymerase chain reaction.
Although DA levels in the adrenals of 24-month-old mice were higher than in 6- and 12-month-old mice, the AD content decreased with age. In such mice, the ratio of DA to NA at 24 months was lower than at 12 months, and the ratio of NA to AD content at 24 months was significantly lower than at 6 months. The mRNA expression ratios in TH, DBH and PNMT in 24-month-old mice were all lower than in 12-month-old mice.
These results strongly suggest that catecholamine synthesis, in general, declines with aging in the adrenal glands of mice and that AD, in particular, undergoes a significant decrease with advancing age.
儿茶酚胺作为重要的生理递质和激素,在某些物种衰老过程中,其在大脑和血浆中的含量明显下降。由于这一观察结果引发了争议,我们使用小鼠来研究肾上腺儿茶酚胺水平和儿茶酚胺合成酶的表达是否会随年龄的增长而发生变化。
从雄性 C57BL/6NCr 小鼠 6、12 和 24 月龄时采集肾上腺。使用高灵敏度的液相色谱法结合过氧草酸化学发光反应检测,测定这些腺体中的儿茶酚胺,如多巴胺(DA)、去甲肾上腺素(NA)和肾上腺素(AD)。采用实时定量聚合酶链反应测定酪氨酸羟化酶(TH)、多巴脱羧酶、多巴胺β羟化酶(DBH)和苯乙醇胺 N-甲基转移酶(PNMT)mRNA 的表达水平。
尽管 24 月龄小鼠肾上腺中的 DA 水平高于 6 月龄和 12 月龄小鼠,但 AD 含量随年龄增长而下降。在这些小鼠中,24 月龄时 DA 与 NA 的比值低于 12 月龄,24 月龄时 NA 与 AD 含量的比值明显低于 6 月龄。24 月龄小鼠的 TH、DBH 和 PNMT 的 mRNA 表达比值均低于 12 月龄小鼠。
这些结果强烈表明,一般来说,儿茶酚胺的合成随着小鼠肾上腺的衰老而下降,特别是 AD 随着年龄的增长而显著下降。