Van Cauter E, Leproult R, Kupfer D J
Department of Medicine, University of Chicago, Illinois 60637, USA.
J Clin Endocrinol Metab. 1996 Jul;81(7):2468-73. doi: 10.1210/jcem.81.7.8675562.
Data from rodent studies indicate that cumulative stress exposure may accelerate senescence and offer a theory to explain differences in the rate of aging. Cumulative exposure to glucocorticoids causes hippocampal defects, resulting in an impairment of the ability to terminate glucocorticoid secretion at the end of stress and, therefore, in increased exposure to glucocorticoids which, in turn, further decreases the ability of the hypothalamo-pituitary-adrenal axis to recover from a challenge. However, the consensus emerging from reviews of human studies is that basal corticotropic function is unaffected by aging, suggesting that the negative interaction of stress and aging does not occur in man. In the present study, a total of 177 temporal profiles of plasma cortisol from 90 normal men and 87 women, aged 18-83 yr, were collected from 7 laboratories and reanalyzed. Twelve parameters quantifying mean levels, value and timing of morning maximum and nocturnal nadir, circadian rhythm amplitude, and start and end of quiescent period were calculated for each individual profile. In both men and women, mean cortisol levels increased by 20-50% between 20-80 yr of age. Premenopausal women had slightly lower mean levels than men in the same age range, primarily because of lower morning maxima. The level of the nocturnal nadir increased progressively with aging in both sexes. An age-related elevation in the morning acrophase occurred in women, but not in men. The diurnal rhythmicity of cortisol secretion was preserved in old age, but the relative amplitude was dampened, and the timing of the circadian elevation was advanced. We conclude that there are marked gender-specific effects of aging on the levels and diurnal variation of human adrenocorticotropic activity, consistent with the hypothesis of the "wear and tear" of lifelong exposure to stress. The alterations in circadian amplitude and phase could be involved in the etiology of sleep disorders in the elderly.
来自啮齿动物研究的数据表明，累积应激暴露可能会加速衰老，并为解释衰老速率差异提供一种理论。累积暴露于糖皮质激素会导致海马体缺陷，从而损害应激结束时终止糖皮质激素分泌的能力，因此会增加糖皮质激素的暴露量，而这反过来又会进一步降低下丘脑 - 垂体 - 肾上腺轴从应激中恢复的能力。然而，对人类研究综述得出的共识是，基础促肾上腺皮质激素功能不受衰老影响，这表明应激与衰老的负面相互作用在人类中不会发生。在本研究中，从7个实验室收集了90名年龄在18 - 83岁的正常男性和87名女性的总共177份血浆皮质醇时间曲线，并进行了重新分析。为每个个体曲线计算了12个参数，这些参数量化了平均水平、早晨最大值和夜间最低点的值及时间、昼夜节律幅度以及静止期的开始和结束。在男性和女性中，20 - 80岁之间平均皮质醇水平增加了20 - 50%。绝经前女性在同一年龄范围内的平均水平略低于男性，主要是因为早晨最大值较低。夜间最低点水平在两性中均随着年龄增长而逐渐升高。女性出现了与年龄相关的早晨高峰期升高，而男性没有。皮质醇分泌的昼夜节律在老年时得以保留，但相对幅度减小，昼夜升高的时间提前。我们得出结论，衰老对人类促肾上腺皮质激素活性的水平和昼夜变化存在明显的性别特异性影响，这与终身暴露于应激的“磨损”假说一致。昼夜节律幅度和相位的改变可能与老年人睡眠障碍的病因有关。
