Tagged research

How Exercise May Help the Brain Grow Stronger

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Physical activity is good for our brains. A wealth of science supports that idea. But precisely how exercise alters and improves the brain remains somewhat mysterious.

A new study with mice fills in one piece of that puzzle. It shows that, in rodents at least, strenuous exercise seems to beneficially change how certain genes work inside the brain. Though the study was in mice, and not people, there are encouraging hints that similar things may be going on inside our own skulls.

For years, scientists have known that the brains of animals and people who regularly exercise are different than the brains of those who are sedentary. Experiments in animals show that, for instance, exercise induces the creation of many new cells in the hippocampus, which is a part of the brain essential for memory and learning, and also improves the survival of those fragile, newborn neurons.

Researchers believe that exercise performs these feats at least in part by goosing the body’s production of a substance called brain-derived neurotropic factor, or B.D.N.F., which is a protein that scientists sometimes refer to as “Miracle-Gro” for the brain. B.D.N.F. helps neurons to grow and remain vigorous and also strengthens the synapses that connect neurons, allowing the brain to function better. Low levels of B.D.N.F. have been associated with cognitive decline in both people and animals. Exercise increases levels of B.D.N.F. in brain tissue.

But scientists have not understood just what it is about exercise that prompts the brain to start pumping out additional B.D.N.F.

So for the new study, which was published this month in the journal eLIFE, researchers with New York University’s Langone Medical Center and other institutions decided to microscopically examine and reverse engineer the steps that lead to a surge in B.D.N.F. after exercise.

They began by gathering healthy mice. Half of the animals were put into cages that contained running wheels. The others were housed without wheels. For a month, all of the animals were allowed to get on with their lives. Those living with wheels ran often, generally covering several miles a day, since mice like to run. The others remained sedentary.

After four weeks, the scientists looked at brain tissue from the hippocampus of both groups of animals, checking for B.D.N.F. levels. As expected, the levels were much higher in the brains of the runners.

But then, to better understand why the runners had more B.D.N.F., the researchers turned to the particular gene in the animals’ DNA that is known to create B.D.N.F. For some reason, the scientists realized, this gene was more active among the animals that exercised than those that did not.

Using sophisticated testing methods, the scientists soon learned why. In both groups of animals, the B.D.N.F. gene was partially covered with clusters of a particular type of molecule that binds to the gene, though in different amounts.

In the sedentary mice, these molecules swarmed so densely over the gene that they blocked signals that tell the gene to turn on. As a result, the B.D.N.F. genes of the sedentary animals were relatively muted, pumping out little B.D.N.F.

But among the runners, the molecular blockade was much less effective. The molecules couldn’t seem to cover and bind to the entire B.D.N.F. gene. So messages from the body continued to reach the gene and tell it to turn on and produce more B.D.N.F.

Perhaps most remarkably, the researchers also found a particular substance in the runners’ brains that fended off the action of these obstructionist molecules. The runners’ brains contained high levels of ketones, which are a byproduct of the breakdown of fat. During strenuous exercise, the body relies in part on fat for fuel and winds up creating ketones, some of which migrate to the brain. (They are tiny enough to cross the blood-brain barrier.) The brain uses these ketones for fuel when blood sugar levels grow low.

But it appears that ketones also cause the molecules that hinder the B.D.N.F. gene to loosen their grip, as the scientists realized when they experimentally added ketones to brain tissue from some of the mice. Afterward, their B.D.N.F. genes were not blocked by nearly as many of the bothersome molecules, and those genes could get on with the job of making B.D.N.F.

None of this occurred in the brains of the sedentary mice.

“It’s incredible just how pervasive and complex the effects of exercise are on the brain,” said Moses Chao, a professor at the Skirball Institute of Biomolecular Medicine at N.Y.U. who oversaw the study.

Whether the same mechanisms that occur in mice occur in our own brains when we exercise is still unknown. But, Dr. Chao pointed out, like the mice, we have more B.D.N.F. in our bodies after exercise. We also create ketones when we exercise, and those ketones are known to migrate to our brains..

Generally, however, this process requires exerting yourself vigorously for an hour or more, after which time your body, having exhausted its stores of sugar, starts burning stored fat and making ketones.

If an hour or more of intense exercise seems daunting — and it does to me — don’t despair. “We are only starting to understand” the many ways in which exercise of any kind and amount is likely to alter our brains, Dr. Chao said. For now, he says, “it’s a very good idea to just keep moving.”

A Decades-Old Study, Rediscovered, Challenges Advice on Saturated Fat

A four-decades-old study — recently discovered in a dusty basement — has raised new questions about longstanding dietary advice and the perils of saturated fat in the American diet.

The research, known as the Minnesota Coronary Experiment, was a major controlled clinical trial conducted from 1968 to 1973, which studied the diets of more than 9,000 people at state mental hospitals and a nursing home.

During the study, which was paid for by the National Heart, Lung and Blood Institute and led by Dr. Ivan Frantz Jr. of the University of Minnesota Medical School, researchers were able to tightly regulate the diets of the institutionalized study subjects. Half of those subjects were fed meals rich in saturated fats from milk, cheese and beef. The remaining group ate a diet in which much of the saturated fat was removed and replaced with corn oil, an unsaturated fat that is common in many processed foods today. The study was intended to show that removing saturated fat from people’s diets and replacing it with polyunsaturated fat from vegetable oils would protect them against heart disease and lower their mortality.

So what was the result? Despite being one of the largest controlled clinical dietary trials of its kind ever conducted, the data were never fully analyzed.

Several years ago, Christopher E. Ramsden, a medical investigator at the National Institutes of Health, learned about the long-overlooked study. Intrigued, he contacted the University of Minnesota in hopes of reviewing the unpublished data. Dr. Frantz, who died in 2009, had been a prominent scientist at the university, where he studied the link between saturated fat and heart disease. One of his closest colleagues was Ancel Keys, an influential scientist whose research in the 1950s helped establish saturated fat as public health enemy No. 1, prompting the federal government to recommend low-fat diets to the entire nation.

“My father definitely believed in reducing saturated fats, and I grew up that way,” said Dr. Robert Frantz, the lead researcher’s son and a cardiologist at the Mayo Clinic. “We followed a relatively low-fat diet at home, and on Sundays or special occasions, we’d have bacon and eggs.”

The younger Dr. Frantz made three trips to the family home, finally discovering the dusty box marked “Minnesota Coronary Survey,” in his father’s basement. He turned it over to Dr. Ramsden for analysis.

The results were a surprise. Participants who ate a diet low in saturated fat and enriched with corn oil reduced their cholesterol by an average of 14 percent, compared with a change of just 1 percent in the control group. But the low-saturated fat diet did not reduce mortality. In fact, the study found that the greater the drop in cholesterol, the higher the risk of death during the trial.

The findings run counter to conventional dietary recommendations that advise a diet low in saturated fat to decrease heart risk. Current dietary guidelines call for Americans to replace saturated fat, which tends to raise cholesterol, with vegetable oils and other polyunsaturated fats, which lower cholesterol.

While it is unclear why the trial data had not previously been fully analyzed, one possibility is that Dr. Frantz and his colleagues faced resistance from medical journals at a time when questioning the link between saturated fat and disease was deeply unpopular.

“It could be that they tried to publish all of their results but had a hard time getting them published,” said Daisy Zamora, an author of the new study and a research scientist at the University of North Carolina at Chapel Hill.

The younger Dr. Frantz said his father was probably startled by what seemed to be no benefit in replacing saturated fat with vegetable oil.

“When it turned out that it didn’t reduce risk, it was quite puzzling,” he said. “And since it was effective in lowering cholesterol, it was weird.”

The new analysis, published on Tuesday in the journal BMJ, elicited a sharp response from top nutrition experts, who said the study was flawed. Walter Willett, the chairman of the nutrition department at the Harvard T.H. Chan School of Public Health, called the research “irrelevant to current dietary recommendations” that emphasize replacing saturated fat with polyunsaturated fat.

Frank Hu, a nutrition expert who served on the government’s 2015 dietary guidelines committee, said the Minnesota trial was not long enough to show the cardiovascular benefits of consuming vegetable oil because the patients on average were followed for only about 15 months. He pointed to a major 2010 meta-analysis that found that people had fewer heart attacks when they increased their intake of vegetable oils and other polyunsaturated fats over at least four years.

“I don’t think the authors’ strong conclusions are supported by the data,” he said.

To investigate whether the new findings were a fluke, Dr. Zamora and her colleagues analyzed four similar, rigorous trials that tested the effects of replacing saturated fat with vegetable oils rich in linoleic acid. Those, too, failed to show any reduction in mortality from heart disease.

“One would expect that the more you lowered cholesterol, the better the outcome,” Dr. Ramsden said. “But in this case the opposite association was found. The greater degree of cholesterol-lowering was associated with a higher, rather than a lower, risk of death.”

One explanation for the surprise finding may be omega-6 fatty acids, which are found in high levels in corn, soybean, cottonseed and sunflower oils. While leading nutrition experts point to ample evidence that cooking with these vegetable oils instead of butter improves cholesterol and prevents heart disease, others argue that high levels of omega-6 can simultaneously promote inflammation. This inflammation could outweigh the benefits of cholesterol reduction, they say.

In 2013, Dr. Ramsden and his colleagues published a controversial paper about a large clinical trial that had been carried out in Australia in the 1960s but had never been fully analyzed. The trial found that men who replaced saturated fat with omega-6-rich polyunsaturated fats lowered their cholesterol. But they were also more likely to die from a heart attack than a control group of men who ate more saturated fat.

Ron Krauss, the former chairman of the American Heart Association’s dietary guidelines committee, said the new research was intriguing. But he said there was a vast body of research supporting polyunsaturated fats for heart health, and that the relationship between cholesterol-lowering and mortality could be deceiving.

People who have high LDL cholesterol, the so-called bad kind, typically experience greater drops in cholesterol in response to dietary changes than people with lower LDL. Perhaps people in the new study who had the greatest drop in cholesterol also had higher mortality rates because they had more underlying disease.

“It’s possible that the greater cholesterol response was in people who had more vascular risk related to their higher cholesterol levels,” he said.

Dr. Ramsden stressed that the findings by he and his colleagues should be interpreted cautiously. The research does not show that saturated fats are beneficial, he said: “But maybe they’re not as bad as people thought.”

The research underscores that the science behind dietary fat may be more complex than nutrition recommendations suggest. The body requires omega-6 fats like linoleic acid in small amounts. But emerging research suggests that in excess linoleic acid may play a role in a variety of disorders including liver disease and chronic pain.

A century ago, it was common for Americans to get about 2 percent of their daily calories from linoleic acid. Today, Americans on average consume more than triple that amount, much of it from processed foods like lunch meats, salad dressings, desserts, pizza, french fries and packaged snacks like potato chips. More natural sources of fat such as olive oil, butter and egg yolks contain linoleic acid as well but in smaller quantities.

Eating whole, unprocessed foods and plants may be one way to get all the linoleic acid your body needs, Dr. Ramsden said.

The Secrets to a Happy Life, From a Harvard Study

What does it take to live a good life?

Surveys show that most young adults believe that obtaining wealth and fame are keys to a happy life. But a long-running study out of Harvard suggests that one of the most important predictors of whether you age well and live a long and happy life is not the amount of money you amass or notoriety you receive. A much more important barometer of long term health and well-being is the strength of your relationships with family, friends and spouses.

These are some of the findings from the Harvard Study of Adult Development, a research project that since 1938 has closely tracked and examined the lives of more than 700 men and in some cases their spouses. The study has revealed some surprising – and some not so surprising – factors that determine whether people are likely to age happily and healthily, or descend into loneliness, sickness and mental decline.

The study’s current director, , outlined some of the more striking findings from the long-running project in a recent TED Talk that has garnered more than seven million views.

“We publish our findings in academic journals that most people don’t read,” Dr. Waldinger, a clinical professor of psychiatry at Harvard Medical School, said in a recent interview. “And so we really wanted people to know that this study exists and that it has for 75 years. We’ve been funded by the government for so many years, and it’s important that more people know about this besides academics.”

The study began in Boston in the 1930s with two very different groups of young men.

In one case, a team of researchers decided to track Harvard college students through adulthood to see what factors played important roles in their growth and success. “They thought there was too much emphasis placed on pathology at the time and that it would be really useful to study people who were doing well in their young adult development,” Dr. Waldinger said. The study recruited 268 Harvard sophomores and followed them closely, with frequent interviews and health examinations. In recent years the study has also incorporated brain scans, blood draws and interviews with the subjects’ spouses and adult children.

At around the same time the study began, a Harvard Law School professor named Sheldon Glueck started to study young men from some of Boston’s poorest neighborhoods, including 456 who managed to avoid delinquency despite coming from troubled homes. Eventually the two groups were merged into one study.

Over the decades, the men have gone into all walks of life. They’ve become lawyers, doctors, businessmen and — in the case of one Harvard student named John F. Kennedy — president of the United States. Others went down different paths. Some became alcoholics, had disappointing careers or descended into mental illness. Those who remain alive today are in their 90s.

Through the years, the study has produced many notable findings. It showed, for example, that to age well physically, the single most important thing you could do was to avoid smoking. It discovered that aging liberals had longer and more active sex lives than conservatives. It found that alcohol was the primary cause of divorce among men in the study, and that alcohol abuse often preceded depression (rather than the other way around).

The study has gone through several directors. Dr. Waldinger, who took over in 2003, is its fourth. He expanded the study so it focused not just on the men but also on their wives and children. The researchers began videotaping the couples in their homes, studying their interactions, and interviewing them separately about nearly every facet of their lives, even day-to-day spats.

As the researchers looked at the factors throughout the years that strongly influenced health and well-being, they found that relationships with friends, and especially spouses, were a major one. The people in the strongest relationships were protected against chronic disease, mental illness and memory decline – even if those relationships had many ups and downs.

“Those good relationships don’t have to be smooth all the time,” Dr. Waldinger said. “Some of our octogenarian couples could bicker day in and day out. But as long as they felt that they could really count on the other when the going got tough, those arguments didn’t take a toll on their memories.”

Dr. Waldinger found a similar pattern among relationships outside the home. The people who sought to replace old colleagues with new friends after retiring were happier and healthier than those who left work and placed less emphasis on maintaining strong social networks.

“Over and over in these 75 years,” Dr. Waldinger said, “our study has shown that the people who fared the best were the people who leaned into relationships with family, with friends and with community.”

Dr. Waldinger acknowledged that the research showed a correlation, not necessarily causation. Another possibility is that people who are healthier and happier to begin with are simply more likely to make and maintain relationships, whereas those who are sicker gradually become more socially isolated or end up in bad relationships.

But he said that by following the subjects for many decades and comparing the state of their health and their relationships early on, he was fairly confident that strong social bonds are a causal role in long-term health and well-being.

So what concrete actions does he recommend?

“The possibilities are endless,” he said. “Something as simple as replacing screen time with people time, or livening up a stale relationship by doing something new together, long walks or date nights. Reach out to that family member you haven’t spoken to in years — because those all-too-common family feuds take a terrible toll on the people who hold the grudges.”

To Reduce the Risk of Alzheimer’s, Eat Fish

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Salmon for sale at the Tsukiji fish market in Tokyo, Japan.

Salmon for sale at the Tsukiji fish market in Tokyo, Japan.Credit Kevin Miyazaki for The New York Times

Eating seafood is linked to a reduced risk of dementia-associated brain changes in people who carry the ApoE4 gene variation, which increases the risk for Alzheimer’s disease. Eating seafood was not linked to similar changes in those who carried other forms of the ApoE gene.

The study, published in JAMA, looked at 286 autopsied brains and also found that eating seafood was linked to increased mercury in the brain, but that mercury levels were not linked to brain abnormalities.

After controlling for age, sex, education and other factors, the researchers found that compared with those who ate less seafood, ApoE4 carriers who had one seafood meal or more a week had lower densities of the amyloid plaques and neurofibrillary tangles typical of Alzheimer’s disease. Over all, they had a 47 percent lower likelihood of having a post-mortem diagnosis of Alzheimer’s.

Consumption of fish oil supplements was not correlated with pathological brain changes.

The lead author, Martha Clare Morris, a professor of epidemiology at Rush University, said that mercury from fish appears to pose little risk for aging people. But, she said, there are studies that show that mercury consumption in pregnancy can cause cognitive problems in babies.

“Most studies in dementia have found that one seafood meal a week is beneficial,” she said, though “they haven’t found that the more you eat, the lower the risk.”