Vinod Ch, Jagota Anita
Neurobiology and Molecular Chronobiology Lab, Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, 500046, India.
Biogerontology. 2016 Nov;17(5-6):859-871. doi: 10.1007/s10522-016-9656-6. Epub 2016 Sep 10.
In mammals suprachiasmatic nucleus (SCN), acts as a light entrainable master clock and by generation of temporal oscillations regulates the peripheral organs acting as autonomous clocks resulting in overt behavioral and physiological rhythms. SCN also controls synthesis and release of melatonin (hormonal message for darkness) from pineal. Nitric Oxide (NO) acts as an important neurotransmitter in generating the phase shifts of circadian rhythms and participates in sleep-wake processes, maintenance of vascular tone as well as signalling and regulating inflammatory processes. Aging is associated with disruption of circadian timing system and decline in endogenous melatonin leading to several physiological disorders. Here we report the effect of aging on NO daily rhythms in various peripheral clocks such as kidney, intestine, liver, heart, lungs and testis. NO levels were measured at zeitgeber time (ZT) 0, 6, 12 and 18 in these tissues using Griess assay in male Wistar rats. Aging resulted in alteration of NO levels as well as phase of NO in both 12 and 24 months groups. Correlation analysis demonstrated loss of stoichiometric interaction between the various peripheral clocks with aging. Age induced alterations in NO daily rhythms were found to be most significant in liver and, interestingly least in lungs. Neurohormone melatonin, an endogenous synchroniser and an antiaging agent decreases with aging. We report further differential restoration with exogenous melatonin administration of age induced alterations in NO daily rhythms and mean levels in kidney, intestine and liver and the stoichiometric interactions between the various peripheral clocks.
在哺乳动物中，视交叉上核（SCN）作为一个可被光调节的主时钟，通过产生时间振荡来调节作为自主时钟的外周器官，从而导致明显的行为和生理节律。SCN还控制松果体中褪黑素（黑暗的激素信号）的合成和释放。一氧化氮（NO）作为一种重要的神经递质，在产生昼夜节律的相移中发挥作用，并参与睡眠-觉醒过程、维持血管张力以及信号传导和调节炎症过程。衰老与昼夜节律系统的紊乱和内源性褪黑素的减少有关，从而导致多种生理紊乱。在此，我们报告衰老对各种外周时钟（如肾脏、肠道、肝脏、心脏、肺和睾丸）中NO每日节律的影响。在雄性Wistar大鼠中，使用格里斯试剂在这些组织的授时时间（ZT）0、6、12和18测量NO水平。衰老导致12个月和24个月组的NO水平以及NO相位发生改变。相关性分析表明，随着衰老，各种外周时钟之间的化学计量相互作用丧失。发现衰老诱导的NO每日节律变化在肝脏中最为显著，有趣的是在肺中最不显著。神经激素褪黑素，一种内源性同步剂和抗衰老剂，随着衰老而减少。我们进一步报告了外源性褪黑素给药对衰老诱导的肾脏、肠道和肝脏中NO每日节律和平均水平的改变以及各种外周时钟之间化学计量相互作用的差异恢复情况。
