Posts Tagged ‘exercise’

Poor physical fitness in middle age might be associated with a smaller brain size later on, according to a study published in an online issue of Neurology.

Brains shrink as people age, and the atrophy is related to cognitive decline and increased risk for dementia, a researcher said, and exercise reduces that deterioration and cognitive decline.

In this study, more than 1,500 people at an average age of 40 and without dementia or heart disease took a treadmill test. Twenty years later, they took another test, along with MRI brain scans. The study found those who didn’t perform as well on the treadmill test — a sign of poor fitness — had smaller brains 20 years later.

Among those who performed lower, people who hadn’t developed heart problems and weren’t using medication for blood pressure had the equivalent of one year of accelerated brain aging. Those who had developed heart problems or were using medication had the equivalent of two years of accelerated brain aging.

Their exercise capacity was measured using the length of time participants could exercise on the treadmill before their heart rate reached a certain level. Researchers measured heart rate and blood pressure responses to an early stage on the treadmill test, which provides a good picture for a person’s fitness level, according to the study author Nicole Spartano, a postdoctoral fellow at the Boston University School of Medicine.

Physical fitness is evolving as a significant factor related to cognitive health in older age. A study published in May 2015 found that higher levels of physical fitness in middle-aged adults were associated with larger brain volumes five years later.

This study shows that for people with heart disease, fitness might be particularly important for prevention of brain aging, Spartano said.

“We found that poor physical fitness in midlife was linked to more rapid brain aging two decades later,” she said. “This message may be especially important for people with heart disease or at risk for heart disease, in which we found an even stronger relationship between fitness and brain aging.”

The researchers also found that people with higher blood pressure and heart rate during exercise were more likely to have smaller brain sizes 20 years later. People with poor physical fitness usually have higher blood pressure and heart rate responses to low levels of exercise compared to people who exercise more, Spartano said

“From other studies, we know that exercise training programs that improve fitness may increase blood flow and oxygen to the brain over the short term,” Spartano said. “Over the course of a lifetime, improved blood flow may have an impact on brain aging and prevent cognitive decline in older age.”

The study suggests promotion of physical fitness during middle age is an important step toward ensuring healthy brain aging.

“The broad message,” Spartano said, “is that health and lifestyle choices that you make throughout your life may have consequences many years later.”

http://www.cnn.com/2016/02/15/health/poor-fitness-smaller-brain/index.html

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By Carina Storrs

If you are intensifying your running regimen in hopes of losing weight, you might be running around in circles: There is a limit to how many calories we can burn through exercise, a new study suggests.

The grim message comes from a small study of a group of 332 adults living in the United States, Jamaica and Africa, some of them more sedentary and some more active. A team of researchers measured their activity level for seven days using an accelerometer, similar to the kind in the Fitbit and other wearable devices, and also measured the number of calories the participants burned over the week.

The researchers found that the participants who moved more also burned more calories, but only up to a point. The most active people hit a plateau and did not burn any more calories than their less-active peers.

Although the researchers did not look at the specific activities that participants were doing, the level on the accelerometer at which calorie burning peters out would be achieved “if you’re walking a couple miles a day, like to work and back, taking the stairs instead of the elevator and trying to exercise a couple times a week,” said Herman Pontzer, associate professor of anthropology at Hunter College, and lead author of the study, which was published on Thursday in the journal Current Biology.

The study is in step with a growing body of research suggesting that burning a bunch of calories is a less realistic weight loss strategy than we might have thought, or hoped. “We can’t push the calories out [value] around too much,” Pontzer said. “Our bodies work very hard to keep it the same.”

It might be time to shift that standard public health message: To lose weight, simply exercise more.

“We would say that ‘If you want to lose weight, you probably ought to focus on changing your diet and watching how much you eat.’ Exercise can help and it’s really important [for health in general], but they are two different tools,” Pontzer said.

The challenge of trying to lose weight just by exercising more is no secret to some clinicians. “This study actually explains a phenomenon that I see quite commonly,” said Dr. Holly F. Lofton, director of the Medical Weight Management Program at NYU Langone Medical Center.

“I see patients training for a marathon and they ask me, ‘Why am I not losing weight?’ ” even though they are exercising more and eating the same number of calories, Lofton said.

People who are increasing their exercise within a less ambitious range, such as going from being sedentary to walking or going from walking to jogging a few miles a day, will probably increase the number of calories they burn proportionally. But “over time, as you do higher levels of activity, you don’t increase your energy expenditure [or calories burned] in a linear way,” she said.

The phenomenon is also in play on the flipside, in terms of calories we take in. “We tend to think that if [patients] eat less than 800 calories, the body’s metabolism shuts down to a level that weight loss slows down quite a bit,” Lofton said.

There are tricks to ratchet up the calorie burn from your workout if you do fall into that higher level of activity.

“If you run all the time, try biking or swimming, and if you bike, try running or swimming, because using different muscles can increase your energy expenditure again,” Lofton said. “It may also be possible to decrease and then increase your activity again and get an increase [in calorie burning],” she said.

And if you think you can necessarily rely on your Fitbit or other device to tell you how many calories you burned, think again: We probably burn proportionally fewer calories as we exercise above a certain level of intensity.

“Activity monitors are going to be wrong at predicting energy expenditure because they aren’t incorporating this adaptation,” Pontzer said.

There’s a hint of good news from the current study. The plateau in how many calories participants burned was higher for those with more body fat. “Body fat is sort of a long-term signal to the body about how active you have to be and how much food is available, so your body might burn more calories,” Pontzer said.

Each of us probably maxes out at a slightly different calorie-burning plateau, Pontzer said. In addition to body fat, it could depend on metabolism, hormone levels, muscle mass and genetic differences.

Pontzer and his colleagues took a close look at the types of calories the participants in the study were burning. They found that the participants did actually continue to burn more and more so-called activity calories as they exercised more, but above a “breaking point,” Pontzer said, their bodies compensated by burning fewer resting calories, which are used for carrying out basic biological functions.

It is as if we have a set number of calories in the bank that our bodies let us burn. If we blow too much of that allowance doing physical activity, our bodies may keep us from spending too many calories doing things like ramping up our immune system or stockpiling reproductive resources.

This strategy may be pretty primitive. “We think this is a really common evolutionary adaptation that all animals use to keep from outstripping their resources and to keep from starving. Your body is listening to your environment and setting an energy expenditure level it can maintain,” Pontzer said.

Pontzer first started to suspect that a system of checks and balances might be in place to control calorie output when he was studying populations of hunter-gatherers in Tanzania.

“The women walk six miles a day, the men walk 10 miles; they are super, super active. It’s impressive when you’re out there with them, and yet their energy expenditures aren’t any different than folks who live much more cushy, sedentary lifestyles,” he said. Pontzer joined up with Amy Luke at Loyola University Chicago and her team, which carried out all the measurements for the current study, to get a better idea what was going.

If it is true that people and animals have evolved to divvy up our finite calorie balance between physical activity and everything else, “we hypothesize that maybe this is one of the things that makes exercise so healthy,” Pontzer said.

It may keep our bodies from spending too much energy on things such as immune function, which could in turn prevent inflammation from going haywire and leading to problems such as heart disease.

http://www.cnn.com/2016/01/28/health/weight-loss-exercise-plateau/index.html

With the pressure for a certain body type prevalent in the media, eating disorders are on the rise. But these diseases are not completely socially driven; researchers have uncovered important genetic and biological components as well and are now beginning to tease out the genes and pathways responsible for eating disorder predisposition and pathology.

As we enter the holiday season, shoppers will once again rush into crowded department stores searching for the perfect gift. They will be jostled and bumped, yet for the most part, remain cheerful because of the crisp air, lights, decorations, and the sound of Karen Carpenter’s contralto voice ringing out familiar carols.

While Carpenter is mainly remembered for her musical talents, unfortunately, she is also known for introducing the world to anorexia nervosa (AN), a severe life-threatening mental illness characterized by altered body image and stringent eating patterns that claimed her life just before her 33rd birthday in 1983.

Even though eating disorders (ED) carry one of the highest mortality rates of any mental illness, many researchers and clinicians still view them as socially reinforced behaviors and diagnose them based on criteria such as “inability to maintain body weight,” “undue influence of body weight or shape on self-evaluation,” and “denial of the seriousness of low body weight” (1). This way of thinking was prevalent when Michael Lutter, then an MD/PhD student at the University of Texas Southwestern Medical Center, began his psychiatry residency in an eating disorders unit. “I just remember the intense fear of eating that many patients exhibited and thought that it had to be biologically driven,” he said.

Lutter carried this impression with him when he established his own research laboratory at the University of Iowa. Although clear evidence supports the idea that EDs are biologically driven—they predominantly affect women and significantly alter energy homeostasis—a lack of well-defined animal models combined with the view that they are mainly behavioral abnormalities have hindered studies of the neurobiology of EDs. Still, Lutter is determined to find the biological roots of the disease and tease out the relationship between the psychiatric illness and metabolic disturbance using biochemistry, neuroscience, and human genetics approaches.

We’ve Only Just Begun

Like many diseases, EDs result from complex interactions between genes and environmental risk factors. They tend to run in families, but of course, for many family members, genetics and environment are similar enough that teasing apart the influences of nature and nurture is not easy. Researchers estimate that 50-80% of the predisposition for developing an ED is genetic, but preliminary genome-wide analyses and candidate gene studies failed to identify specific genes that contribute to the risk.

According to Lutter, finding ED study participants can be difficult. “People are either reluctant to participate, or they don’t see that they have a problem,” he reported. Set on finding the genetic underpinnings of EDs, his team began recruiting volunteers and found 2 families, 1 with 20 members, 10 of whom had an ED and another with 5 out of 8 members affected. Rather than doing large-scale linkage and association studies, the team decided to characterize rare single-gene mutations in these families, which led them to identify mutations in the first two genes, estrogen-related receptor α (ESRRA) and histone deacetylase 4 (HDAC4), that clearly associated with ED predisposition in 2013 (1).

“We have larger genetic studies on-going, including the collection of more families. We just happened to publish these two families first because we were able to collect enough individuals and because there is a biological connection between the two genes that we identified,” Lutter explained.

ESRRA appears to be a transcription factor upregulated by exercise and calorie restriction that plays a role in energy balance and metabolism. HDAC4, on the other hand, is a well-described histone deacteylase that has previously been implicated in locomotor activity, body weight homeostasis, and neuronal plasticity.

Using immunoprecipitation, the researchers found that ESRRA interacts with HDAC4, in both the wild type and mutant forms, and transcription assays showed that HDAC4 represses ESRRA activity. When Lutter’s team repeated the transcription assays using mutant forms of the proteins, they found that the ESRRA mutation seen in one family significantly reduced the induction of target gene transcription compared to wild type, and that the mutation in HDAC4 found in the other family increased transcriptional repression for ESRRA target genes.

“ESRRA is a well known regulator of mitochondrial function, and there is an emerging view that mitochondria in the synapse are critical for neurotransmission,” Lutter said. “We are working on identifying target pathways now.”

Bless the Beasts and the Children

Finding genes associated with EDs provides the groundwork for molecular studies, but EDs cannot be completely explained by the actions of altered transcription factors. Individuals suffering these disorders often experience intense anxiety, intrusive thoughts, hyperactivity, and poor coping strategies that lead to rigid and ritualized behaviors and severe crippling perfectionism. They are less aware of their emotions and often try to avoid emotion altogether. To study these complex behaviors, researchers need animal models.

Until recently, scientists relied on mice with access to a running wheel and restricted access to food. Under these conditions, the animals quickly increase their locomotor activity and reduce eating, frequently resulting in death. While some characteristics of EDs—excessive exercise and avoiding food—can be studied in these mice, the model doesn’t allow researchers to explore how the disease actually develops. However, Lutter’s team has now introduced a promising new model (3).

Based on their previous success with identifying the involvement of ESRRA and HDAC4 in EDs, the researchers wondered if mice lacking ESRRA might make suitable models for studies on ED development. To find out, they first performed immunohistochemistry to understand more about the potential cognitive role of ESRRA.

“ESRRA is not expressed very abundantly in areas of the brain typically implicated in the regulation of food intake, which surprised us,” Lutter said. “It is expressed in many cortical regions that have been implicated in the etiology of EDs by brain imaging like the prefrontal cortex, orbitofrontal cortex, and insula. We think that it probably affects the activity of neurons that modulate food intake instead of directly affecting a core feeding circuit.”

With these data, the team next tried providing only 60% of the normal daily calories to their mice for 10 days and looked again at ESRRA expression. Interestingly, ESRRA levels increased significantly when the mice were insufficiently fed, indicating that the protein might be involved in the response to energy balance.

Lutter now believes that upregulation of ESRRA helps organisms adapt to calorie restriction, an effect possibly not happening in those with ESRRA or HDAC4 mutations. “This makes sense for the clinical situation where most individuals will be doing fine until they are challenged by something like a diet or heavy exercise for a sporting event. Once they start losing weight, they don’t adapt their behaviors to increase calorie intake and rapidly spiral into a cycle of greater and greater weight loss.”

When Lutter’s team obtained mice lacking ESRRA, they found that these animals were 15% smaller than their wild type littermates and put forth less effort to obtain food both when fed restricted calorie diets and when they had free access to food. These phenotypes were more pronounced in female mice than male mice, likely due to the role of estrogen signaling. Loss of ESRRA increased grooming behavior, obsessive marble burying, and made mice slower to abandon an escape hole after its relocation, indicating behavioral rigidity. And the mice demonstrated impaired social functioning and reduced locomotion.

Some people with AN exercise extensively, but this isn’t seen in all cases. “I would say it is controversial whether or not hyperactivity is due to a genetic predisposition (trait), secondary to starvations (state), or simply a ritual that develops to counter the anxiety of weight related obsessions. Our data would suggest that it is not due to genetic predisposition,” Lutter explained. “But I would caution against over-interpretation of mouse behavior. The locomotor activity of mice is very different from people and it’s not clear that you can directly translate the results.”

For All We Know

Going forward, Lutter’s group plans to drill down into the behavioral phenotypes seen in their ESRRA null mice. They are currently deleting ESRRA from different neuronal cell types to pair individual neurons with the behaviors they mediate in the hope of working out the neural circuits involved in ED development and pathology.

In addition, the team has created a mouse line carrying one of the HDAC4 mutations previously identified in their genetic study. So far, this mouse “has interesting parallels to the ESRRA-null mouse line,” Lutter reported.

The team continues to recruit volunteers for larger-scale genetic studies. Eventually, they plan to perform RNA-seq to identify the targets of ESRRA and HDAC4 and look into their roles in mitochondrial biogenesis in neurons. Lutter suspects that this process is a key target of ESRRA and could shed light on the cognitive differences, such as altered body image, seen in EDs. In the end, a better understanding of the cells and pathways involved with EDs could create new treatment options, reduce suffering, and maybe even avoid the premature loss of talented individuals to the effects of these disorders.

References

1. Lutter M, Croghan AE, Cui H. Escaping the Golden Cage: Animal Models of Eating Disorders in the Post-Diagnostic and Statistical Manual Era. Biol Psychiatry. 2015 Feb 12.

2. Cui H, Moore J, Ashimi SS, Mason BL, Drawbridge JN, Han S, Hing B, Matthews A, McAdams CJ, Darbro BW, Pieper AA, Waller DA, Xing C, Lutter M. Eating disorder predisposition is associated with ESRRA and HDAC4 mutations. J Clin Invest. 2013 Nov;123(11):4706-13.

3. Cui H, Lu Y, Khan MZ, Anderson RM, McDaniel L, Wilson HE, Yin TC, Radley JJ, Pieper AA, Lutter M. Behavioral disturbances in estrogen-related receptor alpha-null mice. Cell Rep. 2015 Apr 21;11(3):344-50.

http://www.biotechniques.com/news/Exploring-the-Biology-of-Eating-Disorders/biotechniques-361522.html

There’s been a fast growing body of evidence in the last several years that lack of exercise – or sedentariness – is a major risk factor in health. It’s been linked to heart disease, cancer, and to an early death. And now, a new study finds that lack of exercise may actually be even more of a risk than obesity in early mortality: The researchers calculate that a sedentary lifestyle may actually confer twice the risk of death as being obese. That said, the two are both important and, luckily, closely related: So if you start getting active, you’ll probably lose a little weight along the way, which itself is a very good thing.

The new study looked at data from over 334,000 people who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. Over a period of 12 years, the participants’ height, weight, and waist circumferences were tracked, along with self-reports of activity levels, both at work and in free time. All-cause mortality (i.e., death from any cause) was the main outcome of interest.

It turned out that lack of physical activity was linked to the greatest risk of death – and the greatest reduction in death risk was in the difference between the lowest two activity groups. In other words, just moving from “inactive” to “moderately inactive” showed the largest reduction in death risk, especially for normal weight people, but true for people of all body weights. And, the authors say, just taking a brisk 20-minute walk per day can move you from one category to the other, and reduce the risk of death anywhere from 16% to 30%.

Using a statistical model, the team also calculated that being sedentary may account for double the death risk of obesity. According to their math, of the 9.2 million deaths in Europe in 2008, about 337,000 were attributable to obesity, whereas 676,000 were attributable to sedentariness.

Another takeaway from the study, however, is that waist circumference is a bigger player in mortality risk than overall body weight, which has certainly been suggested by previous studies. Belly fat seems to be disproportionately linked to chronic health issues like heart disease, stroke, diabetes, cancer, and of course, early mortality. So reducing belly fat is always a significant benefit to one’s health.

“This large study is rather complex in its details, but the take-away messages are actually both clear and simple,” says David L, Katz, Director of the Yale University Prevention Research CenterGriffin Hospital. “At any given body weight, going from inactive to active can reduce the risk of premature mortality substantially. At any given level of activity, going from overweight to a more optimal weight can do the same. We have long known that not all forms of obesity are equally hazardous, and this study reaffirms that. Losing weight if you have an excess around the middle, where it is most dangerous, exerts an influence on mortality comparable to physical activity. Losing excess weight that is not associated with a high waist circumference reduces mortality risk, but less — as we would expect.”

But perhaps the main point in all of this is that being active and being a healthy weight are inextricably linked. Though activity by itself can offer an immediate health benefit if you remain overweight, getting active also leads naturally to loss of body weight. “This study reminds that being both fit and unfat are good for health,” says Katz, “and can add both life to years, and years to life. These are not really disparate challenges, since the physical activity that leads to fitness is on the short list of priorities for avoiding fatness as well. The challenge before us now is for our culture to make it easier to get there from here.”

Earlier this month a study showed that the concept of “healthy obesity” may be very misleading, since health markers in an obese person tend to deteriorate over time. Though the current study suggests that fitness may matter more than fatness, the two are really two sides of a coin: It would be silly to become active and not lose weight — and it would be very hard to do, since the one leads to the other. But perhaps given the great benefits of exercise alone, public health campaigns should focus not just on losing weight, but on encouraging people to add just small amounts physical activity to their lives right off the bat, and to see where it goes from there.

http://www.forbes.com/sites/alicegwalton/2015/01/15/is-lack-of-exercise-worse-for-your-health-than-obesity/