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Circadian Rhythms Linked to Aging and Well-Being

Circadian cycles impact health, longevity, and metabolism.

The rising and setting of the sun influences the function of every cell in our bodies. Almost every organism on earth—from single-cell algae to humans—has an internal circadian clock which is a biological timing mechanism that corresponds closely with the 24-hour cycle of light and darkness. Human sleep patterns are largely governed by our internal circadian clock.

In humans and animals, circadian patterns follow a 24-hour cycle which is directed by the circadian control center of the brain, called the suprachiasmatic nucleus (SCN), located in the hypothalamus. The rising and setting of the sun is literally hardwired into our neurobiology.

The inner-workings of the "circadian clock" are complex. The molecular processes behind it have eluded scientists until now. Two new studies from June 2013 have uncovered specific proteins that drive circadian cycles. Although it is possible for circadian cycles to function without external cues, these cycles are influenced primarily by the rhythms of light, temperature, and food availability.

A new study from MIT published in the June 20 issue of Cell shows that a protein called SIRT1—previously shown to protect against diseases of aging—also plays a key role in controlling circadian rhythms. In another study published in the latest issue of the Journal of Neuroscience, Katerina Akassoglou, PhD, and her team at Gladstone found that a specific neurotrophin receptor protein (p75NTR) oscillates in time with the body's natural circadian clock and regulates vital metabolic functions. The discovery of this protein offers new insights into how the circadian clock helps maintain the body's overall metabolic health.

Circadian Rhythms Linked to Aging and Well-Being

Studies in animals have found that when circadian rhythm is thrown off, health problems including obesity and metabolic disorders such as diabetes can arise. People who work night shifts have an increased susceptibility to obesity and diabetes. Researchers at MIT have also discovered a link between a disruption in circadian cycles and aging.

"Just about everything that takes place physiologically is really staged along the circadian cycle," Leonard Guarente senior author of the paper says. "What's now emerging is the idea that maintaining the circadian cycle is quite important in health maintenance, and if it gets broken, there's a penalty to be paid in health and perhaps in aging." Researchers in Guarente's lab at MIT are investigating the relationship between health, circadian function and diet. They suspect that high-fat diets might throw the circadian clock out of whack, which could be counteracted by increased SIRT1 activation.

The researchers at MIT discovered that circadian function disintegrates as mice age. Boosting the levels of SIRT1 levels in the brain helped slow the rate of decay. Conversely, loss of SIRT1 function impairs circadian control in young mice, mimicking what happens in normal aging.

In mice with normal SIRT1 levels, the researchers confirmed previous findings that when the 12-hour light/dark cycle is interrupted, younger mice readjust their circadian cycles much more easily than older ones. However, they showed for the first time that mice with extra SIRT1 do not suffer the same decline in circadian control as they age. SIRT1, which Guarente first linked with aging more than 15 years ago, is a master regulator of cell responses to stress, coordinating a variety of hormone networks, proteins and genes to help keep cells alive and healthy.

Circadian Clocks Directly Impact Metabolic Health

Dr. Akassoglou, a Gladstone researcher, is also a professor of neurology at the University of California, San Francisco who studies circadian cycles. In a new study she found that, "Important metabolic functions are also heavily influenced by circadian clocks, which is why activities such as chronic night-shift work—which can cause a misalignment of this clock—increase one's risk for metabolic and autoimmune diseases such as obesity, Type 2 diabetes, cancer and multiple sclerosis." She adds, "In this study, we pinpointed p75NTR as an important molecular 'link' between circadian clocks and metabolic health."

Originally, p75NTR was only thought to be active in the nervous system. Later studies found that it is active in many cell types throughout the body, suggesting that it impacts a wide range of biological functions. Last year, UCSF researchers discovered that p75NTR was present in the liver and in fat cells, and that it regulates glucose levels in the blood, which is an important metabolic process.

Probably the more important finding about how p75NTR works is when it is produced. Akassoglou and her team found that p75NTR production—like the circadian clock genes themselves—oscillates in a 24-hour cycle that is kept in sync with the cells' natural circadian rhythm.

Experiments in mouse models further supported these findings. However, what was most fascinating, say the researchers, was how a drop in p75NTR levels caused a chain reaction that affected a variety of circadian clock systems. Specifically, the regular oscillations of other circadian genes in the brain and the liver became disrupted, as well as genes known to regulate glucose and lipid metabolism.

"While these findings reveal p75NTR to be an important link between circadian clocks and metabolism, the system is complex, and there are likely other factors at play," said Dr. Akassoglou. "We are currently working to identify the relationship between the circadian clock, metabolism and the immune system, so that one day we could develop therapies to treat diseases influenced by circadian clock disruption—including not only obesity and diabetes, but also potentially multiple sclerosis and even Alzheimer's disease."

Conclusion: Our circadian clocks are thrown out of whack in a modern world.

We have evolved for millennia to have our seasonal sleep-wake cycles reflect sunrise and sunset times. Before the advent of electricity our circadian cycles were directly tuned by Nature. In a modern world our neurobiological clock is short-circuiting as we sleep, wake, and work regardless of sunrise and sunset times, or day and night.

Although June 21st is the summer solstice and longest day of year, the sun actually sets later in the days following the summer solstice. June 23 and 24 are traditionally two of the latest sunset times of the year. Do you feel like your biological clock is affected by when the sun rises and sets? I have literally been getting up with the birds every morning for the past few weeks and am looking forward to sunrise times moving farther past 5am... The older I get, the more sensitive to early morning insomnia I become in the summertime. Have you experienced this phenomenon?

A growing body of evidence suggests that being able to respond to large or small disruptions of the light/dark cycle is important to maintaining healthy metabolic function. Leonard Guarente concludes, "Essentially we experience a mini jet lag every day because the light cycle is constantly changing. The critical thing for us is to be able to adapt smoothly to these jolts." Guarente says, "Many studies in mice say that while young mice do this perfectly well, it's the old mice that have the problem. So that could well be true in humans.”

What can you do to keep your circadian clock in sync without drugs? Previous findings have shown that being exposed to natural light throughout the day not only improves workplace performance but harmonizes your circadian cycles. Please check out my recent Psychology Today post here for some tips on using a light-box to combat sleep disorders if you work in a windowless environment, Seasonal Affective Disorder (SAD), and for more details on the suprachiasmatic nucleus (SCN).

Listen to your body and try to follow the ebb and flow of daylight to keep your circadian rhythms in sync with the season. Also, there is growing evidence that following a lower fat diet may help keep circadian rhythms in sync and improve metabolic health. Keeping your circadian clock in sync with your natural environment will improve well-being, metabolic health, immune function, and help you live longer.