In This Issue
Watch Your Circadian Clock to Help Your Ticker
Biomedical sciences researcher studies links between body clocks and heart disease
BY ANDREW VOWLES
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| Analyzing microarrays and DNA sequences such as these will help biomedical sciences professor Tami Martino learn more about the body’s circadian rhythms and cardiovascular disease. A study co-authored by Martino last year found that allowing your circadian clock to fall out of sync with the 24-hour world can cause heart and kidney disease. Photo by Martin Schwalbe |
Allowing your inner circadian clock to fall out of sync with the 24-hour world outside your body can cause heart disease. That’s the finding of a study last year whose lead author took up a new faculty post at Guelph this spring.
Prof. Tami Martino, Biomedical Sciences, says doctors, nurses, pharmacists — virtually the entire medical profession — need to heed circadian rhythms in diagnosing and treating heart disease patients.
And shift workers, flight crews, patients with sleep disorders and other people with disturbed day-night rhythms should watch for exacerbated cardiovascular problems.
Martino also says researchers who work with human or animal subjects might ask whether their studies account properly for what she calls an ignored but important variable for all creatures.
“We now know that our behaviour, body physiology and molecular processes differ dramatically during the day versus night, and the basis for this is the molecular clock mechanism,” says Martino, who completed an undergraduate degree at McMaster University in her hometown of Hamilton before doing graduate work at the University of Toronto.
“In every cell in our body, we have a clock mechanism that allows us to know what time of day it is. We need it. Without it, we wouldn’t survive on a 24-hour planet.”
Through an intricate mechanism involving hormones and feedback loops, every cell in your body synchronizes itself to the passage of day and night.
Your eyes convey information about light levels to the brain’s hypothalamus. From here, molecular pathways distribute signals throughout the body and help set the clock mechanism in all your cells. This mechanism exists in most creatures. A version also runs in plants, helping to govern key processes such as flowering time.
In healthy humans, the circadian clock keeps everything ticking in sync. Upset the daily rhythm and you introduce stresses that may cause various ailments.
Last year’s paper in the American Journal of Physiology — co-authored with Toronto researchers — found that disrupting circadian rhythms in hamsters led to cardiovascular and renal disease.
Martino scrolls through slides on her desktop to display the evidence. Your heart rate and blood pressure fall at night and increase by day in a predictable curve. Platelet clumping happens more often early in the day, increasing the risk of heart attacks at that time. Indeed, she says, most hospital admissions for heart attacks occur in the morning.
Even more striking are several slides showing abnormal heart and kidney cells and early death in mutant hamsters. The mutation causes the rodents to live by a 22-hour clock, leading to fragmented sleeping and activity patterns. When the Toronto team imposed an appropriate day-night cycle — a bit of a challenge, Martino concedes, because “Canadian Tire doesn’t have a lot of 22-hour-world timers” — the hamsters turned out healthy.
Crank up the microscope and you can see what happens at the level of individual genes. In 2004, she and her collaborators published the first paper using gene microarrays and bioinformatics technologies to show how genes in heart tissue switch on and off from night to day, with as much regularity as lights flicking on and off in time-lapse photos of downtown office towers.
“The study showed that gene expression in the heart is remarkably different during the day versus the night,” says Martino. That work appeared in the Journal of Molecular Medicine.
The findings suggest a few practical questions for her. Why do hospitals keep lights on in intensive-care units around the clock? Do drug prescriptions stress the optimum time of day for dosing up? Are blood tests for heart disease indicators best taken during the day or at night (a key question for so-called “non-dippers” whose blood pressure fails to fall at night in the accustomed pattern)? What other “night light” biomarkers might doctors use?
“It’s like a whole world opens to you when you start looking at the other end of the day,” she says. “If you know what to look for, you get more information.”
She hopes her work might provide more tools for doctors and patients.
Martino has similar questions for researchers using human and animal subjects for experiments. Few clinical trials account for changing efficacy of therapies over time, she says.
Considering circadian rhythms might lead to better-designed animal-care facilities. Martino shows off a notebook with sketches of housing cabinets whose more efficient day-night cycles may reduce stress for animals and improve monitoring for researchers.
She says her work may also benefit people with sleep disorders, including sleep apnea, as well as nurses, flight attendants and shift workers on abnormal day-night cycles. Shifting hormone activity affects heart disease and cancer.
Ultimately, she says, accounting for circadian rhythms and finding genetic markers will bring us a step closer to personalized medicine.
That brings her studies close to home. She and her husband, Kevin, have two children — Nick, 14, and Rachel, 9. There’s a long history of heart disease on her maternal grandfather’s side, says Martino, whose genealogical research recently yielded a 300-page family history.
“They all died young of heart attacks,” she says. “I guess that makes you wonder what happens. Why is it contributing to be such a major economic burden?”
Her research is funded by the Heart and Stroke Foundation of Ontario.