Gubin D G, Gubin G D, Waterhouse J, Weinert D
Department of Biology, Medical Academy, Tyumen, Russia.
Chronobiol Int. 2006;23(3):639-58. doi: 10.1080/07420520600650612.
The present study is part of a more extensive investigation dedicated to the study and treatment of age-dependent changes/disturbances in the circadian system in humans. It was performed in the Tyumen Elderly Veteran House and included 97 subjects of both genders, ranging from 63 to 91 yrs of age. They lived a self-chosen sleep-wake regimen to suit their personal convenience. The experiment lasted 3 wks. After 1 control week, part of the group (n=63) received 1.5 mg melatonin (Melaxen) daily at 22:30 h for 2 wks. The other 34 subjects were given placebo. Axillary temperature was measured using calibrated mercury thermometers at 03:00, 08:00, 11:00, 14:00, 17:00, and 23:00 h each of the first and third week. Specially trained personnel took the measurements, avoiding disturbing the sleep of the subjects. To evaluate age-dependent changes, data obtained under similar conditions on 58 young adults (both genders, 17 to 39 yrs of age) were used. Rhythm characteristics were estimated by means of cosinor analyses, and intra- and inter-individual variability by analysis of variance (ANOVA). In both age groups, the body temperature underwent daily changes. The MESOR (36.38+/-0.19 degrees C vs. 36.17+/-0.21 degrees C) and circadian amplitude (0.33+/-0.01 degrees C vs. 0.26+/-0.01 degrees C) were slightly decreased in the elderly compared to the young adult subjects (p<0.001). The mean circadian acrophase was similar in both age groups (17.19+/-1.66 vs. 16.93+/-3.08 h). However, the inter-individual differences were higher in the older group, with individual values varying between 10:00 and 23:00 h. It was mainly this phase variability that caused a decrease in the inter-daily rhythm stability and lower group amplitude. With melatonin treatment, the MESOR was lower by 0.1 degrees C and the amplitude increased to 0.34+/-0.01 degrees C, a similar value to that found in young adults. This was probably due to the increase of the inter-daily rhythm stability. The mean acrophase did not change (16.93 vs. 16.75 h), although the inter-individual variability decreased considerably. The corresponding standard deviations (SD) of the group acrophases were 3.08 and 1.51 h (p<0.01). A highly significant correlation between the acrophase before treatment and the phase change under melatonin treatment indicates that this is due to a synchronizing effect of melatonin. Apart from the difference in MESOR, the body temperature rhythm in the elderly subjects undergoing melatonin treatment was not significantly different from that of young adults. The data clearly show that age-dependent changes mainly concern rhythm stability and synchronization with the 24 h day. A single daily melatonin dose stabilizes/synchronizes the body temperature rhythm, most probably via hypothermic and sleep-improving effects.
本研究是一项更为广泛调查的一部分,该调查致力于研究和治疗人类昼夜节律系统中与年龄相关的变化/紊乱。研究在秋明老年退伍军人之家进行,纳入了97名年龄在63至91岁之间的男女受试者。他们按照自己选择的睡眠 - 清醒作息方式生活,以方便个人生活。实验持续3周。在1周的对照期后,部分受试者(n = 63)在22:30每天服用1.5毫克褪黑素(美拉松),持续2周。另外34名受试者服用安慰剂。在第一周和第三周的每天03:00、08:00、11:00、14:00、17:00和23:00,使用校准后的水银温度计测量腋窝温度。由经过专门培训的人员进行测量,避免打扰受试者睡眠。为评估与年龄相关的变化,使用了在类似条件下获取的58名年轻成年人(年龄在17至39岁之间的男女)的数据。通过余弦分析估计节律特征,通过方差分析(ANOVA)评估个体内和个体间的变异性。在两个年龄组中,体温都有每日变化。与年轻成年人相比,老年人的中值(MESOR)(36.38±0.19℃对36.17±0.21℃)和昼夜振幅(0.33±0.01℃对0.26±0.01℃)略有降低(p<0.001)。两个年龄组的平均昼夜峰值相位相似(17.19±1.66对16.93±3.08小时)。然而,老年组的个体间差异更大,个体值在10:00至23:00之间变化。主要是这种相位变异性导致了日节律稳定性下降和组振幅降低。服用褪黑素后,中值降低了0.1℃,振幅增加到0.34±0.01℃,与年轻成年人中的值相似。这可能是由于日节律稳定性增加。平均峰值相位没有变化(16.93对16.75小时),尽管个体间变异性显著降低。组峰值相位的相应标准差(SD)分别为3.08和1.51小时(p<0.01)。治疗前的峰值相位与褪黑素治疗下的相位变化之间存在高度显著的相关性,表明这是由于褪黑素的同步作用。除了中值的差异外,接受褪黑素治疗的老年受试者的体温节律与年轻成年人的体温节律没有显著差异。数据清楚地表明,与年龄相关的变化主要涉及节律稳定性以及与24小时昼夜的同步。每日单次服用褪黑素可稳定/同步体温节律,很可能是通过降温及改善睡眠的作用。