RESPONSIVENESS OF THE AGING CIRCADIAN CLOCK TO LIGHT

老化生物钟对光的反应

• 批准号: 7376832
• 负责人: SUSAN J BENLOUCIF
• 金额: $ 17.87万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376832
• 关键词: RESPONSIVENESS; AGING; CIRCADIAN; CLOCK; LIGHT

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our long-term goal is to understand the basis of, and develop effective therapies for, chronic sleep disturbances in older adults. Chronic sleep disturbance is reported by nearly 50% of the elderly population. Common in this age group is an advance in the phase of sleep, accompanied by sleep maintenance insomnia and early morning awakenings. This can shorten the total sleep time and lead to daytime fatigue and impaired performance. The advance in sleep is associated with an advance in the timing of the circadian core body temperature (CBT) rhythm, indicating an advance in the timing of the circadian clock. The cause of the advance in phase is not known. However, preliminary data from our laboratory show that elderly subjects do not phase delay following exposure to light before the CBT minimum, a time that induces maximal delays in young subjects. The first goal of this proposal is to better understand the mechanism underlying this age-related change in responsiveness of the clock to light. Our long-term goal is to understand the basis of, and develop effective therapies for, chronic sleep disturbances in older adults. Chronic sleep disturbance is reported by nearly 50% of the elderly population. Common in this age group is an advance in the phase of sleep, accompanied by sleep maintenance insomnia and early morning awakenings. This can shorten the total sleep time and lead to daytime fatigue and impaired performance. The advance in sleep is associated with an advance in the timing of the circadian core body temperature (CBT) rhythm, indicating an advance in the timing of the circadian clock. The cause of the advance in phase is not known. However, preliminary data from our laboratory show that elderly subjects do not phase delay following exposure to light before the CBT minimum, a time that induces maximal delays in young subjects. The first goal of this proposal is to better understand the mechanism underlying this age-related change in responsiveness of the clock to light. The first Specific Aim will test the hypothesis that the circadian clock becomes less responsive to light with age. This hypothesis will be tested by comparing the magnitude of phase shifts of rhythms of melatonin, thyrotropin (TSH), and CBT in young and older adults following exposure to light at three different times (or phases) relative to the temperature minimum. The second Specific Aim will test the hypothesis that the phase response curve to light is altered with age. This hypothesis will be tested by plotting the direction and magnitude of phase shifts relative to the initial phase of melatonin, TSH, and CBT to generate the phase response curves to light. The direction and magnitude of phase shifts of the phase markers will be compared in young and older adults to determine whether age affects the phase dependent response of the clock to light. The second goal of this proposal is to assess whether it is possible to compensate for age-related changes in the responsiveness of the aging circadian clock to light, by increasing the intensity of the light exposure or by pharmacological treatment with the calcium channel antagonist nimodipine (Specific Aim 3). The proposed experiments will provide a vast amount of data in which to better understand the effect of age on circadian rhythms and sleep, and lead to improved treatments for circadian rhythm and sleep disorders in older adults.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。我们的长期目标是了解老年人的慢性睡眠障碍的基础，并开发有效的疗法。据报道，近50％的老年人口报告了慢性睡眠障碍。在这个年龄段，常见的是睡眠阶段的进步，伴随着睡眠失眠和清晨觉醒。这可以缩短总睡眠时间，并导致白天疲劳和表现受损。睡眠的进展与昼夜节律体温（CBT）节奏的时间的进步有关，这表明昼夜节律时钟的进步。尚不清楚阶段前进的原因。但是，我们实验室的初步数据表明，老年受试者在最低CBT之前暴露在光线后不会相位延迟，这是诱发年轻受试者最大延迟的时间。 该提案的第一个目标是更好地了解时钟响应能力的这种与年龄相关的变化的机制。我们的长期目标是了解老年人的慢性睡眠障碍的基础，并开发有效的疗法。据报道，近50％的老年人口报告了慢性睡眠障碍。在这个年龄段，常见的是睡眠阶段的进步，伴随着睡眠失眠和清晨觉醒。这可以缩短总睡眠时间，并导致白天疲劳和表现受损。睡眠的进展与昼夜节律体温（CBT）节奏的时间的进步有关，这表明昼夜节律时钟的进步。尚不清楚阶段前进的原因。但是，我们实验室的初步数据表明，老年受试者在最低CBT之前暴露在光线后不会相位延迟，这是诱发年轻受试者最大延迟的时间。 该提案的第一个目标是更好地了解时钟响应能力的这种与年龄相关的变化的机制。第一个特定目的将检验以下假设：昼夜节律随着年龄的增长而对光的反应较低。该假设将通过比较褪黑激素，甲状腺激素（TSH）和CBT的节奏相变的相位相对于温度最小值的三个不同时间（或相）的暴露后，将进行检验。第二个特定目的将检验以下假设，即随着年龄的增长，对光的相响应曲线会改变。该假设将通过绘制相对于褪黑激素，TSH和CBT的初始相的相移方向和幅度来检验，以生成光向响应曲线。在年轻人和老年人中，将比较相位标记的相移的方向和大小，以确定年龄是否影响时钟对光的相位依赖性响应。 该提案的第二个目标是评估是否有可能通过增加光暴露的强度或对钙通道拮抗剂Nimodipine的药理治疗来补偿与年龄相关的昼夜节律对照明的反应性变化（特定目标3）。 拟议的实验将提供大量数据，以更好地了解年龄对昼夜节律和睡眠的影响，并改善对老年人的昼夜节律和睡眠障碍的治疗方法。