Functional Genomics Unit, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):15036-41. doi: 10.1073/pnas.1207768109. Epub 2012 Aug 27.
A convenient way to estimate internal body time (BT) is essential for chronotherapy and time-restricted feeding, both of which use body-time information to maximize potency and minimize toxicity during drug administration and feeding, respectively. Previously, we proposed a molecular timetable based on circadian-oscillating substances in multiple mouse organs or blood to estimate internal body time from samples taken at only a few time points. Here we applied this molecular-timetable concept to estimate and evaluate internal body time in humans. We constructed a 1.5-d reference timetable of oscillating metabolites in human blood samples with 2-h sampling frequency while simultaneously controlling for the confounding effects of activity level, light, temperature, sleep, and food intake. By using this metabolite timetable as a reference, we accurately determined internal body time within 3 h from just two anti-phase blood samples. Our minimally invasive, molecular-timetable method with human blood enables highly optimized and personalized medicine.
一种方便估计体内时间(BT)的方法对于时间疗法和时间限制喂养至关重要,这两种方法分别利用体时信息在药物给药和喂养期间使效力最大化并使毒性最小化。此前,我们提出了一种基于多个小鼠器官或血液中昼夜节律波动物质的分子时间表,以便仅从少数几个时间点采集的样本估计体内时间。在这里,我们将这种分子时间表的概念应用于估计和评估人体的内部时间。我们构建了一个 1.5 天的人类血液样本中代谢物波动的参考时间表,采样频率为 2 小时,同时控制活动水平、光照、温度、睡眠和食物摄入的混杂影响。通过使用这种代谢物时间表作为参考,我们仅从两个反相血液样本中就可以在 3 小时内准确确定内部时间。我们使用人类血液的微创分子时间表方法可实现高度优化和个性化的医学。