When she was amidst master’s studies at University of Chicago, Constanza Cortes Rodriguez recalled feeling burned out. “Nothing was happening in the lab and I was overwhelmed,” Rodriguez says. This is when she was a member of in the university’s Ballroom and Latin Dance Association and was captivated by salsa and the bachata. She soon began to practice for up to nine hours per week, perfecting moves with heels of three inches.

“The Second Half of Life” study co-authored by the AARP as well as National Geographic


In a telephone and online survey of 2,580 people 18 and over, those aged 18 and over were more receptive to the importance of exercise when as compared to those who are in their 30s, 40s and 50s. The respondents also said that brain health is the top priority for everyone of any age.

Researchers are currently trying to understand what exercises do to improve brain function in order to create more effective treatments and recommendations.

“The final goal is to create a drug which mimics the effects of exercise on the brain” Rodriguez says. This is especially relevant in people who aren’t able to simply hop on a treadmill like people who have mobility problems or those who are frail.

The brainy benefits of being healthy

Research from decades ago connects fitness and physical activity to positive brain changes in a range of settings.

For children, for instance physical activity is associated with improved cognitive performance as determined by IQ tests as well as academic achievements. Studies on the epidemiology of older adults reveal that regular exercise can reduce the chance to develop Alzheimer’s. Studies of imaging have shown that the size of the hippocampus — a region of the brain that is crucial to memory and learning – is larger in those who are athletically fit than their more sedentary counterparts. The subjects, who ranged from the age range of 59-81 were also able to perform well on tests of spatial memory.

Furthermore, exercise aids those with brain functions that have already been declining It also improves learning focus, memory, and attention for those suffering from Alzheimer’s disease that is in its early stages or schizophrenia, as well as brain injuries. Psychologists have observed the benefits of exercise for their patientstoo.

“Exercise can help alleviate symptoms of depression and anxiety in significant manners,” says Juli Fraga who is a psychologist from San Francisco. “It’s such a beneficial thing that psychotherapists frequently prescribe it to patients and some even offer walk-and talk therapy.”

Despite the growing evidence for the benefits of exercise to the brain, a rationale for the mechanism behind these benefits is still elusive for researchers. As scientists gain more knowledge about the changes that occur to the brain when it agesor the brain is turned on by itself during the course of neurodegenerative disorders, new theories on how exercise affects the vital organ are developing.

Two papers from Henriette van Praag who is a postdoc in The Salk Institute for Biological Studies in California. The papers looked at the adult brains of mice who took part in a race on a wheel, compared to those who did not. The results revealed for the first time in mammals that exercising triggers the creation neuronal cells, known as neurogenesis which is a process that occurs inside the brains mature mice. These changes were followed by improvement in spatial memory as well as learning.

Van Praag, who is currently an assistant professor in the Florida Atlantic University’s Stiles-Nicholson Brain Institute, says there was a bit of serendipity involved in the finding. In a previous study researchers observed evidence that a element of an environment that was enriched–where mice were exposed to a variety of stimulations, including areas to hide or toys — produced new neurons. Then she set out to discover the primary aspect. “Running was really only one of the variables in my research,” she laughs.

“Van Praag’s work is crucial in establishing the connection between running and the development of neurons and improved brain function. This is important not just for the neurobiology field but also in opening the door for researchers in the field of exercise and muscle to investigate the interplay between muscle training, exercise, as well as the brain.” Says Handschin.

In 2002, Bruce Spiegelman, a cell biologist at the Dana-Farber Cancer Institute and Harvard Medical School and Harvard Medical School, was researching a protein known as PCG1-alpha which controls the metabolism of your body through switching genes off and on. He found that increasing the levels of the protein in mice increased the strength of their muscles as well as redder and filled with blood vessels. It was like the mice were working hard at the gym without walking on a treadmill.

In the same time, researchers began to understand that the muscles that move produced myokines and other hormones that are released into bloodstreams and offer benefits to distant organs. The discovery of PGC1-alpha resulted in Spiegelman to ask what the protein does to make muscle appear to be active so “maybe it will also trigger muscles to release substances which are made in the course of exercise.” It could utilize the protein to help discover the molecules that are responsible for the beneficial changes in the immune system and metabolism that exercise causes.

The search culminated in 2012, when Spiegelman and his colleagues discovered Irisin, a myokine that is produced by muscle exercise. They realized that irisin turns the white part of fat to beige. Because beige fat is calorie-burning, unlike white fat which stores them, Spegelman believed that it could be the key ingredient in the way exercise can combat weight gain and diabetes.

Further pieces of the puzzle were put in place the following year, when Christiane Wrann, who was then postdoctoral researcher with Spiegelman discovered that muscles were “talking” with the brain in exercises. When muscles produce irisin and increase the levels of another protein, called”the brain-derived neural factor (BDNF) located in the hippocampus, which is one of the first areas of the brain to change during neurodegenerative illnesses. The hippocampus is where BDNF enhances the health and development of neurons and synapses making them more mature and increasing synaptic plasticity.

In the past year, Wrann who is currently a neuroscientist at Massachusetts General Hospital and Harvard Medical School studied the role of irisin during exercising and cognitive performance. Her team tested mice that are genetically engineered to be deficient in irisin to mice that produced the chemical. After exercising the mice with control performance better at a task which relies in learning and spatial awareness. However, the mice that lack irisin did not show the same improvements, suggesting that irisin may be the factor that boosts the cognitive abilities.

The team of Wrann’s examined brains of mice, they discovered that both mice produced neurons when they exercise. However, the neurons in mice deficient in irisin were abnormal, which affected their ability to create connections. When the gene that produces the protein irisin was introduced back to mice’s brains that lack the protein, they were able to distinguish between two patterns that were similar and this is a trait humans consider useful in finding a car in a parking space, for instance.

Exercise and neurodegenerative diseases

The team of Wrann also found that irisin may be a factor in protecting against neurodegeneration. Researchers bred mice deficient in irisin and showed Alzheimer’s-like symptoms. The mice that were doubly affected had symptoms faster than mice with only Alzheimer’s disease. Furthermore, they showed improvements in their cognitive abilities when the production of irisin was restored.

Wrann believes that the way the irisin can help is that it helps reduce inflammation caused by malfunctions within our brain’s immune system. The system is comprised predominantly of cells known as microglia and astrocytes. They are typically responsible for the reduction of brain infections and clearing of debris following an injury. As we age, however the cells may remain inactive after the immediate threat has gone away and affect neuronal function initially by disrupting the connections between neurons, and later through the killing of cells.

This process results in chronic inflammation of the brain, which has been linked to a variety of neurological diseases, including Alzheimer’s disease and Parkinson’s. However, lab mouse models treated by irisin experienced lower inflammation of their hippocampuses and their astrocytes and microglia decreased which suggests that irisin was able to reduce the haywire immune response.

What do these results mean to human beings? Maybe, based on preliminary research conducted by Wrann’s lab as well as from other labs. Irisin has the same molecular structure that is found in humans and mice She says this suggests it has similar functions for both species.

The findings have exciting implications regarding the neuro-protective effects of exercise, since research has shown an increase in irisin levels in blood of people after an exercise. On the other hand studies of post-mortems of the brains of patients with Alzheimer’s show an increase of 70 percent in the irisin precursor molecule, compared to healthy controls of the same age and suggests that irisin might be neuroprotective.

From a therapeutic point of view, “irisin certainly is promising,” says Handschin, “especially due to the research on its effect on the brain.” However, he warns that irisin isn’t yet able to pass the rigorous tests that define the path towards drug development. “Whether it’s successful in humans is yet to be determined.”

Depression, anxiety and mood disorders

Handschin is particularly fascinated by the interaction between muscles activity, mood, and motivation. In an unpublished study his team examined the impact that certain chemicals produced through exercise affect mice’s ability to run on a wheel. Animals without these components can run, however, they do not choose to. This is a characteristic of mice, who usually go for up to six miles per day.

“There is something in muscles that sends signals back in the brain that somehow decreases the desire to run just for the sake of running,” Handschin says.

The field’s promise for treatments of mood disorders–particularly severe depression–also interests Spiegelman, who calls it one of medicine’s great unmet needs. “Severe depression has been identified as the leading reason for suicide and is particularly prevalent among young individuals,” he says. He and his colleagues are studying the impact of irisin on depression induced by anxiety in research models using mice.

The brain’s dialogue in exercise isn’t restricted to muscles. The interactions with proteins that are released from the fat, liver and bone, helps the brain , allowing us to sharpen our thinking, prevent depression, and so on.

With promising pharmacological options like irisin , among others, being considered The U.A.’s Rodriguez is convinced that “we’re nearing the end of a new period of discovery that is eventually going to be translated into clinical practice.”

However, the rapid growth of research on brain-muscle crosstalk can bring both benefits as well as challenges, says Karina Alvina who is an associate professor in neuroscience of the University of Florida College of Medicine. The salient molecules impact multiple systems in a variety of ways, meaning the potential for their use is vast However, untangling their diverse interactions can be a challenge. Making a drug that doesn’t result in unintended consequences is the biggest issue, she adds.

However, Alvina finds a measure of optimism in the studies she and her colleagues are conducting. This research suggests “the surroundings and our lifestyle choices have a huge impact on how our bodies age” Alvina says. It’s in our ability to age more healthy and live a longer and more fulfilling quality of life over the course of time.

“So If I had to make a statement that I would recommend, it’s to keep yourself active, even if it’s just only walking for a few minutes every day. If you’re able to, you should.”