ALTERED RHYTHMS IN AGING--MECHANISMS AND RESTORATION OF FUNCTION

在金仓鼠中，有明显的与年龄相关的变化 牵引和自由运行下昼夜节律的表达 条件，以及生物钟系统对 各种光刺激和非光刺激。 期间进行的研究 之前的资助期在三个领域提供了重要的观察结果 关于这种与年龄相关的变化的发展， 纠正策略的根本机制和可能的方法。 拟议的研究将建立在这些发现的基础上：1）确定 各种与年龄有关的变化的发展年表 生物钟系统，2）确定生理机制 生物钟系统中与年龄相关的潜在变化以及 3) 测试 扭转或减弱具体对策的有效性 衰老对昼夜节律的影响。 特别是各种 将测试关于血清素和神经肽的作用的假设 Y，以及松果体及其激素褪黑激素的影响， 与年龄相关的昼夜节律系统变化。 对策涉及 用褪黑激素治疗或改变诱导光的强度 将采用暗循环来检验与年龄相关的变化的假设 昼夜节律系统中的变化可以减弱、延迟或逆转。 贯穿始终 拟议的研究，衰老对五种表达的影响 不同的节律（即车轮行驶行为、总运动活动、 饮酒行为、体温和循环褪黑激素水平），以及 关于昼夜节律起搏器通过以下任一方式进行相移的能力 光刺激或非光刺激将在仓鼠中确定。 它是 预期阐明年龄的生理基础 昼夜节律功能及其机制的相关变化 各种纠正策略的有效性，将带来新的见解 昼夜节律的调节和组织及其 与环境刺激的相互作用。 这些研究也有望 导致治疗、预防或延迟的新临床方法 老年人群的昼夜节律和睡眠紊乱。

In the golden hamster, there are pronounced age-related changes in the expression of circadian rhythm under both entrained and free-running conditions, as well as in the response of the circadian clock system to a variety of photic and non-photic stimuli. Studies performed during the previous grant period have provided important observations in three areas pertaining to the development of such age-related alterations, their underlying mechanisms and possible approaches for corrective strategies. The proposed studies will build on these findings to 1) determine the chronology of the development of various age-related changes in the circadian clock system, 2) to determine the physiological mechanisms underlying age-related changes in the circadian clock system and 3) to test the efficacy of specific countermeasures to reverse or attenuate the effects of aging on circadian rhythmicity. In particular, various hypotheses will be tested regarding the role of serotonin and neuropeptide Y, as well as the influence of the pineal gland and its hormone melatonin, in age-related changes in the circadian system. Countermeasures involving treatment with melatonin or altering the strength of the entraining light- dark cycle will be employed to test the hypothesis that age-related changes in the circadian system can be attenuated, delayed or reversed. Throughout the proposed studies, the effects of aging on the expression of five different rhythms (i.e., wheel-running behavior, total locomotor activity, drinking behavior, body temperature and circulating melatonin levels), and on the ability of the circadian pacemaker to be phase shifted by either photic or non-photic stimuli, will be determined in hamsters. It is anticipated that the elucidation of the physiological basis for age- related changes in circadian function, and of the mechanisms which underlie the efficacy of various corrective strategies, will lead to new insights into the regulation and organization of circadian rhythmicity and of its interaction with environmental stimuli. These studies are also expected to lead to new clinical approaches for treating, preventing or delaying disturbances of circadian rhythms and sleep in older human populations.