Exercise Hormones for the Brain

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A brand new study from Harvard Medical School has been published, shedding some light on the benefits of exercise and aging.

We all know “exercise is good for us.” 

Most people know that regular exercise is helpful for maintaining a healthy weight, and also keeps our bones and muscles strong so that we can stay mobile longer into old age. Some of us may have heard that exercise can reduce your risk of cognitive decline. Until now, however, there was very little information on how exercise was producing these benefits to the brain.

Past studies reported that when we exercise, certain cells in the body produce more of a protein called FNDC5. FNDC5 is known to activate neuroprotective genes in the hippocampus, the brain region in charge of memory formation [1]. Part of FNDC5 can be cleaved off to form a hormone called irisin, which is released into the bloodstream.

What the recent study by Harvard Medical School found is that irisin is the mediator in the effect of exercise on cognition [1].

The study’s researchers created “knockout mice”, whose bodies do not make any irisin regardless of exercise. As hypothesized, when these knockout mice were exercised, it had no effect on cognitive performance. When irisin was administered to the brain of knockout mice (and control mice), cognitive performance was improved. In fact, it improved enough to indicate irisin as the active moiety explaining exercise’s effect on the brain. 

While there were many other elements to the study (which you can read here: https://www.nature.com/articles/s42255-021-00438-z#citeas), these data show a clear role for irisin in the cognitive benefits of exercise [1]. 

Exercise, however, is one very natural way to make more of this powerful hormone. 

Exercise Hormones for the Body

Exercise for the body is so much more than burning calories or bodybuilding. As we age, exercise is about maintaining our mobility and energy levels for better quality and quantity of life. Exercise can also have an effect on the hormones your body produces, maintaining healthy digestion and metabolism into old age.

Being physically active has been shown to help boost levels of muscle-maintaining hormones that decline with age, such as testosterone [2], growth hormone [3,4], and IGF-1 [4]. 

Most important, however, is the relationship between exercise and insulin. Insulin, a hormone secreted by the pancreas, is arguably the most crucial metabolic hormone. It allows our cells to take in glucose for energy production. 

We need insulin, but we need a balance. Poor eating habits, overindulgence in alcohol, and lack of regular exercise can all permanently dysregulate insulin production and secretion. When insulin levels are too high, or cells become insensitive to insulin’s signals, it puts your metabolic and cardiovascular health at risk [5]. 

Luckily, exercise can reduce the amount of insulin in our circulation and increase our insulin sensitivity [6]. Many types of physical activity have been found to increase insulin sensitivity and reduce insulin levels, including aerobic exercise, strength training, and endurance exercise [7,8]. 

We often associate poor metabolic health insulin resistance with diet alone, but research has shown that obese individuals have been able to increase insulin sensitivity with regular exercise, without caloric restriction [8].  

“How does this work?” You may be wondering. The mechanism connecting exercise and insulin sensitivity is mediated, at least in part, by adiponectin [9]. Adiponectin is a hormone secreted by adipose (fat) tissue, and its targets are the liver and skeletal muscle, where it regulates energy metabolism and insulin sensitivity. Circulating adiponectin levels increase over time with regular exercise, but only when the exercise is truly “chronic” or regular [9]. 

To take advantage of adiponectin’s effect on insulin sensitivity, you must make exercise a part of your routine. Hitting the gym hard every once in a while will not have the same effect.


  1. https://www.nature.com/articles/s42255-021-00438-z
  2. https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.13-245480
  3. https://journals.physiology.org/doi/full/10.1152/jappl.1999.87.2.498
  4. https://journals.humankinetics.com/view/journals/ijsnem/20/1/article-p21.xml
  5. https://www.proquest.com/openview/2a564aafae5f5759c45bb0889c5a855e/1?pq-origsite=gscholar&cbl=2044869
  6. https://www.sciencedirect.com/science/article/pii/S1877065718314830
  7. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2000-8847
  8. https://onlinelibrary.wiley.com/doi/full/10.1038/oby.2004.95
  9. https://pubmed.ncbi.nlm.nih.gov/25275268/