ALTERED RHYTHMS IN AGING--MECHANISMS AND RESTORATION OF FUNCTION

衰老节律的改变——机制和功能恢复

• 批准号: 6299348
• 负责人: FRED W TUREK
• 金额: $ 16.94万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-15 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6299348
• 关键词: age difference; aging; biological clocks; body physical activity; body temperature; chordate locomotion; circadian rhythms; environmental adaptation; hamsters; hormone regulation /control mechanism; hormone therapy; hypothalamus; melatonin; neuropeptide Y; neuropeptide receptor; neuropharmacology; nonhuman therapy evaluation; photostimulus; pineal body; serotonin; suprachiasmatic nucleus; triazolam

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.

在金仓鼠中，有明显的年龄相关的变化， 在牵引和自由运行下的昼夜节律表达 条件，以及在生理时钟系统的响应， 各种光和非光刺激。 研究期间进行的研究 上一个赠款期在三个方面提供了重要的观察结果 关于这种年龄相关的变化的发展， 纠正战略的基本机制和可能办法。 拟议的研究将建立在这些发现的基础上，以1）确定 各种年龄相关变化的发展年表 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 采取具体反措施扭转或削弱 衰老对昼夜节律的影响。 特别是，各种 关于血清素和神经肽的作用的假设将被检验 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的变化。 反措施， 用褪黑激素治疗或改变夹带光的强度- 将采用暗周期来检验与年龄有关的变化的假设， 在昼夜节律系统中的作用可以被减弱、延迟或逆转。 在整个 提出的研究，对五个表达的影响， 不同的节奏（即，轮跑行为，总的运动活动， 饮酒行为、体温和循环褪黑激素水平），以及 昼夜节律起搏器的能力， 光或非光刺激，将在仓鼠中确定。 是 预期阐明年龄的生理基础- 昼夜节律功能的相关变化，以及 各种纠正策略的有效性，将导致新的见解 昼夜节律的调节和组织， 与环境刺激的相互作用。 这些研究也有望 导致新的临床方法，用于治疗，预防或延迟 老年人的昼夜节律和睡眠紊乱。