Rhythms of our Lives: Takeaways from the UF Circadian Symposium

It isn’t everyday (well, never) that you get to hear a Nobel Prize winning scientist speak at your University. For one, these scientific Goliaths are rare. They’re also busy, and usually traveling to important conferences and seminars worldwide. Luckily, the University of Florida has several researchers in the field of Circadian Biology — conveniently, the scientific area in which the 2017 Nobel Prize in Physiology and Medicine was awarded.

That prize was awarded to Michael W. Young, Michael Rosbach, and Jeffrey C. Hall (each man shared 1/3 of the nearly 9 million dollar payout), for “their discoveries of molecular mechanisms controlling the circadian rhythm.”

Michael W. Young gives the keynote lecture at U

Circadian rhythms (“circa” = around, “dia” = 24 hours) are biological processes underlying every single process in our body. The complexities of these molecular events is beyond the scope of this article, and beyond the scope of many people outside of Young and various chronobiologists. Mechanisms notwithstanding, the importance of circadian rhythms in our daily life — influencing activity, feeding/fasting, sleeping, and mood — cannot be understated.

A panel of various specialists in the field of chronobiology/circadian rhythms gathered to present data and directions at the University of Florida for the first annual “Circadian Symposium”. Here, I provide some takeaways in what could possibly be the future of preventative medicine, public health, and human physiology, all related to the rhythms of our lives.

A “simple” mechanisms of how the circadian clock is regulated

Biology is Beautifully Congruent

In the keynote lecture, Young began with a personal anecdote; a plaintive, reflective dive into his “introduction” into circadian biology (which, at the time he “discovered” it, wasn’t even a real topic at all). Noting early observations of the rhythmic variation in activity of flowers and honeybees, Young eloquently painted a picture for the audience — life is rhythmic. As humans, we think we are quite unique (and we are, but not as unique as we think). However, initial observations and now key modern insights into biology point to just a few main regulators of internal rhythms that are conserved among many species.

Young presented pictures of the Mirabilis flower (“four o’ clocks”) before and after his walk — a natural observation of circadian rhythms at work

Precise changes in the periodicity of a few genes, leading to a profound change in physiology and even psychology (mood is influenced by circadian processes also). Lost in translation among the jargon of feedback loops, transcriptional regulation, and chryptochrome gene synthesis was a simple message — sometimes life can be so simple, and so beautiful.

Rather than a scientific interest, this resonated with me on a personal (spiritual?) level. How profound that my physiology, in many ways, differs only slightly from that of a blooming flower or a bee signaling the position food through an intricate dance routine? I like think that my complicated wiring and free will drive much of my daily behavior, but it seems, just like the flora and fauna of the earth, I’m regulated by some larger master clock.

“Dancing” behavior of bees is observed to fluctuate with time of day and orientation of food

Disrupted Internal Rhythms Underlie many modern diseases

It is inarguable that modern day and its allowance for us to live “24 hour days” has resulted in profound public and individual health issues. Sleep, namely, has been sacrificed for work, school, and play. Circadian biology is now allowing us to understand, on a molecular level, how disruption of our internal rhythms is casually contributing to many disorders in modern society and the increasing prevalence of disease. Most of us are no longer in line with how our biological rhythm “evolved” to function. Cosmology and Biology were so generous in giving us the rising and setting of the sun an eloquent zeitgeber; which we now largely regard as irrelevant.

Carrie Partch, Ph.D (UCSD) discussed the pathogenesis of disease and its relation to the circadian clock. When our rhythms are synced with the external environment, we optimize energy utilization and leverage our ability to “survive” in the world. While this may have had more importance for “prey” type species to optimize fitness and survival, it is nonetheless an important them for human biology.

Disrupting rhythms in mice, the preferred model for studying circadian biology currently, leads to psychiatric disorders, metabolic disorders (diabetes, obesity), cardiovascular disease, and cancer. How? It seems like a crucial process involves regulation of DNA damage and repair by the body. Disrupting rhythms, disrupting repair, leads ultimately to a dysfunctional system which is a perfect foundation for development of cancer.

In the top image, the mouse’s internal clocks are “synced”. Circadian dysruption occurs when the body and brain clocks are misaligned.

That disruption of rhythms is tied to disease is also intrinsically obvious. What happens when you lack sleep, sleep at the wrong time, or engage in shift work (as around 25% of Americans do)? Dysregulated metabolism, altered appetite, lack of desire to exercise or engage in healthy habits — all of these “symptoms” of an out of line clock can be tied to the development of disease. The parallel increase of sleep loss and disease in modern society is a powerful correlation, suggesting that we need pay more attention to our internal clocks.

Medicine will take advantage of Circadian Rhythms (and already is)

While chronological time is important, “cellular time,” Tami Martino, Ph.D (Guelph) states is equally if not more important for proper function of our physiology. Modern medicine currently ignores the fact that circadian rhythms play a significant role in the treatment and prevention of many diseases. For instance, the recovery process of hospital patients post-surgery has largely ignored the influence of cellular clocks. Citing that in-patients often share a room or are housed in a more or less constantly lit environment, surrounded by the beeps and alerts of medical devices — Martino illustrated that circadian dysruption likely reduces the ability of many to return to health.

Martino and colleagues have published papers suggesting that maintaining normal day and night cycles in hospital ICUs for patients after a heart attack may facilitate recovery. Simple fixes to busy environment such as an ICU, and taking patient care into consideration, could have life-saving effects.

Chronotherapy also seems to be the next frontier in “precision medicine”. Knowing that we have biological clocks in all of our cells, from our arteries to our kidneys, allows us to understand how each of these organs regulated itself — and tailor medication to target these organs at their point of highest susceptibility. For instance, heart drugs are often prescribed to be taken in the morning, for convenience, without any consideration to biological time or internal clocks. However, the biological rhythms of many hormones related to blood pressure and heart health seem to be regulated better when certain drugs are given at night, before bedtime. Cardiovascular events (heart attack ,stroke) occur disproportionately in the morning — so targeting the nighttime modulation of the cardiovascular system, and the morning surge in blood pressure, can lessen the occurrence of these events and possibly save lives. Targeted blood pressure medication is just one effective example of how chronotherapy will advance how we approach and treat health and disease, and many other interventions such as diet are now being tied back to circadian rhythms.

The rhythms of our lives — so complex, yet so seemingly straightforward. The future of health, longevity and disease will benefit from the knowledge that, above all, what humans need is to maintain connection to our biological underpinnings. What could be more simple than that?

Sources

Michael W. Young — Nobel Lecture: Time Travels: A 40 Year Journey from Drosophila´s Clock Mutants to Human Circadian Disorders”. Nobelprize.org. Nobel Media AB 2014. Web. 16 May 2018.

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