By GRETCHEN REYNOLDS

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Gretchen Reynolds on the science of fitness.

As a clinical psychologist and sleep researcher at Northwestern University’s Feinberg School of Medicine, Kelly Glazer Baron frequently heard complaints from aggrieved patients about exercise. They would work out, they told her, sometimes to the point of exhaustion, but they would not sleep better that night.

Dr. Baron was surprised and perplexed. A fan of exercise for treating sleep problems, but also a scientist, she decided to examine more closely the day-to-day relationship between sweat and sleep.

What she and her colleagues found, according to a study published last week in The Journal of Clinical Sleep Medicine, is that the influence of daily exercise on sleep habits is more convoluted than many of us might expect and that, in the short term, sleep may have more of an impact on exercise than exercise has on sleep.

To reach that conclusion, Dr. Baron and her colleagues turned to data from a study of exercise and sleep originally published in 2010. For that experiment, researchers had gathered a small group of women (and one man) who had received diagnoses of insomnia. The volunteers were mostly in their 60s, and all were sedentary.

Then the researchers randomly assigned their volunteers either to remain inactive or to begin a moderate endurance exercise program, consisting of three or four 30-minute exercise sessions per week, generally on a stationary bicycle or treadmill, that were performed in the afternoon. This exercise program continued for 16 weeks.

At the end of that time, the volunteers in the exercise group were sleeping much more soundly than they had been at the start of the study. They slept, on average, about 45 minutes to an hour longer on most nights, waking up less often and reporting more vigor and less sleepiness.

But had the novice exercisers experienced immediate improvements in their sleep patterns, Dr. Baron wondered? And, on a day-to-day basis, had working out on any given day produced better sleep that night?

Boring deep into the data contained in the exercising group’s sleep diaries and other information for the new study, Dr. Baron discovered that the answer to both questions was a fairly resounding no. After the first two months of their exercise program, the exercising volunteers (all of them women) were sleeping no better than at the start of the study. Only after four months of the program had their insomnia improved.

They also rarely reported sleeping better on those nights when they had had an exercise session. And perhaps most telling, they almost always exercised for a shorter amount of time on the days after a poor night’s sleep.

In other words, sleeping badly tended to shorten the next day’s workout, while a full-length exercise session did not, in most cases, produce more and better sleep that night.

At first glance, these results might seem “a bit discouraging,” Dr. Baron said. They also would seem to be at odds with the earlier conclusion that four months of exercise improved insomniacs’ sleep patterns, as well as a wealth of other recent science that typically has found that regular exercise lengthens and deepens sleep.

But, Dr. Baron pointed out, most of these other studies employed volunteers without existing sleep problems. For them, exercise and sleep seem to have a relatively uncomplicated relationship. You work out, fatigue your body and mind, and sleep more soundly that night.

But people with insomnia and other sleep disturbances tend to be “neurologically different,” Dr. Baron said. “They have what we characterize as a hyper-arousal of the stress system,” she said. A single bout of exercise on any given day “is probably not enough to overcome that arousal,” she explained, and potentially could even exacerbate it, since exercise is itself a physical stressor.

Eventually, however, if the exercise program is maintained, Dr. Baron said, the workouts seem to start muting a person’s stress response. Her or his underlying physiological arousal is dialed down enough for sleep to arrive more readily, as it did in the original 2010 experiment.

Of course, both of these studies were small, involving fewer than a dozen exercising volunteers, all of them middle-aged or older women. “We think the findings would apply equally to men,” Dr. Baron said. But that idea has yet to be proven.

Likewise, it is impossible to know yet the sleep-related impacts of workouts of different types (like weight training), intensities or timing, including morning or late-evening sessions.

Still, the preliminary message of these findings is heartening. If you habitually experience insomnia and don’t currently exercise, Dr. Baron said, start. Don’t, however, expect that you will enjoy or even complete workouts that occur on the day after a broken night’s sleep, or that you will sleep better hours after you’ve exercised.

The process is more gradual and less immediately gratifying than the sleep-deprived might wish. But the benefits do develop. “It took four months” in the original study, Dr. Baron said, but at that point the exercising volunteers “were sleeping at least 45 minutes more a night.” “That’s huge, as good as or better” than most current treatment options for sleep disturbances, including drugs, she said.

KS

By GRETCHEN REYNOLDS

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Gretchen Reynolds on the science of fitness.

Exercise promotes health, reducing most people’s risks of developing diabetes and growing obese. But just how, at a cellular level, exercise performs this beneficial magic — what physiological steps are involved and in what order — remains mysterious to a surprising degree.

Several striking new studies, however, provide some clarity by showing that exercise seems able to drastically alter how genes operate.

Genes are, of course, not static. They turn on or off, depending on what biochemical signals they receive from elsewhere in the body. When they are turned on, genes express various proteins that, in turn, prompt a range of physiological actions in the body.

One powerful means of affecting gene activity involves a process called methylation, in which methyl groups, a cluster of carbon and hydrogen atoms, attach to the outside of a gene and make it easier or harder for that gene to receive and respond to messages from the body. In this way, the behavior of the gene is changed, but not the fundamental structure of the gene itself. Remarkably, these methylation patterns can be passed on to offspring – a phenomenon known as epigenetics.

What is particularly fascinating about the methylation process is that it seems to be driven largely by how you live your life. Many recent studies have found that diet, for instance, notably affects the methylation of genes, and scientists working in this area suspect that differing genetic methylation patterns resulting from differing diets may partly determine whether someone develops diabetes and other metabolic diseases.

But the role of physical activity in gene methylation has been poorly understood, even though exercise, like diet, greatly changes the body. So several groups of scientists recently set out to determine what working out does to the exterior of our genes.

The answer, their recently published results show, is plenty.

Of the new studies, perhaps the most tantalizing, conducted principally by researchers affiliated with the Lund University Diabetes Centre in Sweden and published last month in PLoS One, began by recruiting several dozen sedentary but generally healthy adult Swedish men and sucking out some of their fat cells. Using recently developed molecular techniques, the researchers mapped the existing methylation patterns on the DNA within those cells. They also measured the men’s body composition, aerobic capacity, waist circumference, blood pressure, cholesterol levels and similar markers of health and fitness.

Then they asked the men to start working out. Under the guidance of a trainer, the volunteers began attending hourlong spinning or aerobics classes approximately twice a week for six months. By the end of that time, the men had shed fat and inches around their waists, increased their endurance and improved their blood pressure and cholesterol profiles.

Less obviously, but perhaps even more consequentially, they also had altered the methylation pattern of many of the genes in their fat cells. In fact, more than 17,900 individual locations on 7,663 separate genes in the fat cells now displayed changed methylation patterns. In most cases, the genes had become more methylated, but some had fewer methyl groups attached. Both situations affect how those genes express proteins.

The genes showing the greatest change in methylation also tended to be those that had been previously identified as playing some role in fat storage and the risk for developing diabetes or obesity.

“Our data suggest that exercise may affect the risk for Type 2 diabetes and obesity by changing DNA methylation of those genes,” says Charlotte Ling, an associate professor at Lund University and senior author of the study.

Meanwhile, other studies have found that exercise has an equally profound effect on DNA methylation within human muscle cells, even after a single workout.

To reach that conclusion, scientists from the Karolinska Institute in Stockholm and other institutions took muscle biopsies from a group of sedentary men and women and mapped their muscle cell’s methylation patterns. They then had the volunteers ride stationary bicycles until they had burned about 400 calories. Some rode strenuously, others more easily.

Afterward, a second muscle biopsy showed that DNA methylation patterns in the muscle cells were already changing after that lone workout, with some genes gaining methyl groups and some losing them. Several of the genes most altered, as in the fat cell study, are known to produce proteins that affect the body’s metabolism, including the risk for diabetes and obesity.

Interestingly, the muscle cell methylation changes were far more pronounced among the volunteers who had ridden vigorously than in those who had pedaled more gently, even though their total energy output was the same.

The overarching implication of the study’s findings, says Juleen Zierath, a professor of integrative physiology at the Karolinska Institute and senior author of the study, is that DNA methylation changes are probably “one of the earliest adaptations to exercise” and drive the bodily changes that follow.

Of course, the intricacies of that bogglingly complex process have yet to be fully teased out. Scientists do not know, for instance, whether exercise-induced methylation changes linger if someone becomes sedentary, or if resistance training has similar effects on the behavior of genes. Nor is it known whether these changes might be passed on from one generation to the next. But already it is clear, Dr. Ling says, that these new findings “are additional proof of the robust effect exercise can have on the human body, even at the level of our DNA.”

KS

How Exercise Can Calm Anxiety
By GRETCHEN REYNOLDS
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Phys Ed

Gretchen Reynolds on the science of fitness.

In an eye-opening demonstration of nature’s ingenuity, researchers at Princeton University recently discovered that exercise creates vibrant new brain cells — and then shuts them down when they shouldn’t be in action.

For some time, scientists studying exercise have been puzzled by physical activity’s two seemingly incompatible effects on the brain. On the one hand, exercise is known to prompt the creation of new and very excitable brain cells. At the same time, exercise can induce an overall pattern of calm in certain parts of the brain.

Most of us probably don’t realize that neurons are born with certain predispositions. Some, often the younger ones, are by nature easily excited. They fire with almost any provocation, which is laudable if you wish to speed thinking and memory formation.

But that feature is less desirable during times of everyday stress. If a stressor does not involve a life-or-death decision and require immediate physical action, then having lots of excitable neurons firing all at once can be counterproductive, inducing anxiety.

Studies in animals have shown that physical exercise creates excitable neurons in abundance, especially in the hippocampus, a portion of the brain known to be involved in thinking and emotional responses.

But exercise also has been found to reduce anxiety in both people and animals.

How can an activity simultaneously create ideal neurological conditions for anxiety and leave practitioners with a deep-rooted calm, the Princeton researchers wondered?

So they gathered adult mice, injected them with a substance that marks newborn cells in the brain, and for six weeks, allowed half of them to run at will on little wheels, while the others sat quietly in their cages.

Afterward, the scientists determined each group’s baseline nervousness. Given access to cages with open, well-lighted areas, as well as shadowy corners, the running mice were more willing to cautiously explore and spend time in open areas, an indication that they were more confident and less anxious than the sedentary animals.

The researchers also checked the brains of some of the runners and the sedentary mice to determine how many and what varieties of new neurons they contained.

As expected, the runners’ brains teemed with many new, excitable neurons. The sedentary mice’s brains also contained similar, volatile newborn cells, but not in such profusion.

The runners’ brains, however, also had a notable number of new neurons specifically designed to release the neurotransmitter GABA, which inhibits brain activity, keeping other neurons from firing easily. In effect, these are nanny neurons, designed to shush and quiet activity in the brain.

In the runners’ brains, there were large new populations of these cells in a portion of the hippocampus, the ventral region, associated with the processing of emotions. (The rest of the hippocampus, the dorsal region, is more involved with thinking and memory.)

What role these nanny neurons were playing in the animals’ brains and subsequent behavior was not altogether clear.

So the scientists next gently placed the remaining mice in ice-cold water for five minutes. Mice do not enjoy cold water. They find immersion stressful and anxiety-inducing, although it is not life-threatening.

Then the scientists checked these animals’ brains. They were looking for markers, known as immediate early genes, that indicate a neuron has recently fired.

They found them, in profusion. In both the physically fit and the sedentary mice, large numbers of the excitable cells had fired in response to the cold bath. Emotionally, the animals had become fired up by the stress.

But with the runners, it didn’t last long. Their brains, unlike those of the sedentary animals, showed evidence that the shushing neurons also had been activated in large numbers, releasing GABA, calming the excitable neurons’ activity and presumably keeping unnecessary anxiety at bay.

In effect, the runners’ brains had responded to the relatively minor stress of a cold bath with a quick rush of worry and a concomitant, overarching calm.

What all of this suggests, says Elizabeth Gould, director of the Gould Lab at Princeton, who wrote the paper with her graduate student Timothy Schoenfeld, now at the National Institute of Mental Health, and others, “is that the hippocampus of runners is vastly different from that of sedentary animals. Not only are there more excitatory neurons and more excitatory synapses, but the inhibitory neurons are more likely to become activated, presumably to dampen the excitatory neurons, in response to stress.” The findings were published in The Journal of Neuroscience.

It’s important to note, she adds, that this study examined long-term training responses. The runners’ wheels had been locked for 24 hours before their cold bath, so they would gain no acute calming effect from exercise. Instead, the difference in stress response between the runners and the sedentary animals reflected fundamental remodeling of their brains.

Of course, as we all know, mice are not men or women. But, Dr. Gould says, other studies “show that physical exercise reduces anxiety in humans,” suggesting that similar remodeling takes place in the brains of people who work out.

“I think it’s not a huge stretch,” she concludes, “to suggest that the hippocampi of active people might be less susceptible to certain undesirable aspects of stress than those of sedentary people.”

Phys Ed

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