Reading today's 2017 Nobel laureates in physiology/medicine (Ref. 1, 2,3 ) brought me back-tracking almost 25 years ago in New York City.
You didn't know what you missed until very late in your career. You go by instinct at spatiotemporal situation. I didn't see it's coming back in 1993 when Michael Young offered me a position at his Rockefeller University National Lab of Timing - I remember everything was fine except he didn't want me to go for mammalian system but sticker only with Drosophila. His amazing cheerful smile still vividly appears in front of me - what a nice fellow! He's been so prompted at responding to e-mail, very impressive, given his position as VP Rockefeller University and many other responsibilities worldwide.
I didn't have patience in those years as I's strong-headed for my freedom to choose - mammalian systems only direction. In reality, Drosophila led principles can be later used for patients (Ref. 3). This Cell paper can help TCM figure out such as "Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging" -
Western medicine uses the term “circadian rhythms” to describe these asleep patterns. Chinese Medicine uses the theory of the Chinese clock to describe a similar set of biological clock timing for different organs (activity). For example,
The Traditional Chinese (TCM) medicine has discovered that the liver is most active between 1-3am. The liver's daily programming assumes an early dinner and bedtime.
In Traditional Chinese Medicine it is believed that each organ has its point of ... 1-3am is the time of the Liver and a time when the body should be alseep.
www.the-scientist.com › The Scientist › April 2017 Issue › Features
Apr 1, 2017 - But timing flu vaccine delivery would be straightforward to implement. ... notice of
the body's internal rhythms, timed therapies are still the exception to the rule. .... are revealing that timing medications to the body's internal clock ...
1984 年,霍尔和 罗斯巴什(波士顿的布兰迪斯大学)和洛克菲洛大学的 迈克尔·杨成功地分离出了 period 基因。他们把这个基因编码的蛋白其名为“PER”。他们发现,在晚上 ,PER 蛋白会在果蝇体内积累,到了白天又会被分解。并且发现 PER蛋白 的浓度会循环震荡,周期为 24 小时,和昼夜节律相同。他们猜测PER 蛋白可以让 period 基因失去活性。也就是PER蛋白 和 period 基因之间形成了一个抑制反馈的环路,PER蛋白 可以抑制基因合成自己,这样就形成了一个连续循环的完整节律。当period基因有活性的时候,可以合成period mRNA,然后进入细胞质后开始合成PER蛋白。PER蛋白又会进入细胞核,逐渐积累,抑制period的活性。period基因经过了一个完整的24小时周期,就形成了一个抑制性的反馈机制,形成了昼夜节律(见下图)。
period基因反馈条件的简单示意图
2, TIM蛋白基因:timeless----辅助PER蛋白工作
1994 年,洛克菲洛大学的 迈克尔·杨 发现了第二个节律基因:timeless。之前虽然已经发现PER 蛋白的功能,有一个关键环节是从细胞质进入细胞核才能抑制 period 基因。但是它是如何进入细胞核的呢?实际上Timeless 可以编码 TIM蛋白,可以帮助PER进入细胞核。迈克尔·杨做了一个漂亮的实验,发现 TIM 会结合到 PER 上,然后两个蛋白可以一起进入细胞核,并且在那里抑制 period 基因的活性(如下图)。
Decades of lab-animal studies connect health and longevity to dramatic caloric restriction. Scientists continue to replicate these animal studies in their quest to figure out what causes aging. One of these scientists is Paolo Sassone-Corsi, the director of the Center for Epigenetics & Metabolism at the University of California, Irvine. He’s the lead author of a paper published in August in the journal Cell that shows how our biological clock affects metabolism.
四位一体, 四愿读写博文 Postscript(epilogue) for governing all my blog posts
独立的时空, 自由的思写。劳作 (Labor)、艺术 (art)、游戏 (game)、学问 (knowledge), 四位一体; 四愿读写博文: 正义(Justice)、良知 (conscience)、自由 (freedom)、独立 (independence)- leading to integrity, compassion, and mutual respect 。照镜验心,久而久之习惯自然, 我手写我心,写出心安而淡然、端然、坦然。
I can't ask or practice wisdom as I believe it's not by gain of your own effort but given by God like kindness, grace and mercy.
劳作(劳工),艺术,游戏,学问(知识)-
我不能要求或实践获得智慧,因为我相信这智慧不是因为你自己的努力而得到的,而是像上帝的慈爱,恩典和怜悯所给予的。