Irisin: Another Exercise Molecule

By Ram Rao, Ph.D., Principal Research Scientist for Apollo Health

Any form of physical exercise, from walking to swimming to hiking to gardening to dancing, reduces the risk for Alzheimer’s disease (AD). Physical exercise increases cerebral blood flow and upregulates BDNF protein, promoting the growth, maturation, and maintenance of nerve cells. In addition to BDNF, now there is news about yet another protein that may confer the benefits of exercise on cognitive function. In a recent study, scientists showed that strength training induces the production of a neurohormone called ‘Irisin’ that is responsible for mediating the cognitive benefits.

The Bredesen Seven (or “B7”) involves seven distinct yet complementary strategies to optimize brain health. One of the strategies that are recommended for the prevention or reversal of cognitive decline is physical exercise. Physical exercise and the other six strategies create a powerful synergy that allows the brain to heal and be more resilient. Any form of physical exercise is beneficial — everything from walking to swimming to hiking to gardening to dancing — reduces the risk for AD. Furthermore, several research studies show that even those with the highest risk for AD can reduce their chances or delay the onset of developing it by combining physical exercise with other healthy lifestyle strategies.

A recent study found that participants at risk for memory loss were protected against cognitive decline by walking 8,900 steps a day. While this may sound like a lot of effort, doing it regularly makes it much easier. Beyond its specific effects on the brain, physical exercise helps maintain a healthy body mass index (BMI), reduces insulin resistance, inflammation, the risk for heart disease and stroke, and improves blood pressure, all of which results in reducing the risk for AD. It also reduces stress and anxiety while improving mood and sleep. Aerobic exercise and strength training are equally important, especially as we age. Each type activates different mechanisms, thus protecting against cognitive decline through different but converging pathways.

Older adults with higher aerobic fitness have better preservation of overall brain volume, increased cortical thickness (greater thickness is associated with more neurons and improved cognition), and greater white matter integrity (white matter is tissue in the brain that helps transmit signals), leading to higher levels of executive function including critical thinking and planning skills. Aerobic exercise increases cerebral blood flow and upregulates BDNF protein. BDNF promotes the survival of nerve cells by playing a role in the growth, maturation (differentiation), and maintenance of these cells. In addition, BDNF is involved in the repair of the central nervous system following a brain injury. Furthermore, aerobic exercise stimulates the glymphatic system — a waste disposal system for the brain. Beta-amyloid and other brain toxins are cleared through this pathway.  

Strength training also improves brain volume, function, and cognition, particularly executive functioning. Strength training also prevents and remediates skeletal muscle mass loss and strength (sarcopenia) that occurs with aging. Sarcopenia is strongly correlated with cognitive decline. Strength training also prevents loss of bone, reduces bone fracture risk, and decelerates biological aging. Adults who have a regular practice of strength training have enhanced long-term memory, fewer white matter lesions in the brain, an improved gait, better balance, and more easily perform daily activities.

In addition to BDNF, there is news about yet another protein that may confer the benefits of exercise on cognitive function. In a study published last year, scientists showed that strength training induces the production of a neurohormone called ‘Irisin’ that is responsible for mediating the cognitive benefits. Using mouse models of AD, researchers showed that genetic deletion of irisin impairs exercise-induced cognitive function. External administration of irisin improved cognitive abilities. The irisin-treated mice performed better on the cognitive tests and displayed reduced neuroinflammation compared to untreated mice. The researchers were further encouraged by the fact that irisin treatment was effective in mouse models even after the development of significant AD pathology. Moreover, irisin could easily cross the blood-brain barrier to act on the brain. The results suggest that exercise may improve cognitive performance by yet another mechanism involving the irisin protein.

Irisin is identical in mice and people. Its blood levels in people have also been shown to rise with strength training and endurance exercises. Thus, it could help to treat a variety of cognitive disorders. Since irisin blocks neuroinflammation directly, it could also have beneficial effects on neurodegenerative diseases beyond just Alzheimer’s. While studies to test irisin as an intervention for preventing AD or cognitive decline in humans have not yet been done, few studies have examined the relationship between irisin levels and cognitive function in humans.

Compared to people without cognitive impairment, irisin levels in the spinal fluid were significantly lower in people with late-stage AD and those with Lewy body dementia. In an observational study that included AD patients and people without dementia, those with higher irisin levels in the spinal fluid had higher cognitive function, higher BDNF levels, and lower amyloid deposits. Thus, higher levels of irisin in the brain appear to be associated with better brain health. As exciting and promising as irisin may be for cognitive health or dementia prevention, it is important to note that treatment with irisin or its derivatives has not yet been tested in humans. 

Thus, exercise is the best option to increase irisin levels naturally. In a study that compared different forms of activities, high-intensity interval training (HIIT-short bursts of intensive training intermixed with less intense recovery periods) increased irisin levels more than moderate-intensity continuous exercise. This may partly explain why researchers noted that HIIT improves cognition function in older adults with the greatest improvements seen in speed processing and executive function. A word of caution-HIIT can easily be performed to a lesser intensity. Anyone can benefit from lots of movement throughout the day, punctuated with occasional bursts of intense elevations. Exercise can be inexpensive and accessible to everyone. So boost your irisin levels naturally by getting plenty of exercise. Remember, the more active you are, the better you’ll feel physically and mentally, and the more you’ll want to exercise.