How Exercise Affects Your Genes, and More

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Brief, vigorous exercise causes immediate structural and chemical changes in the DNA molecules within your muscles that benefit your health

Endurance training also produces beneficial genetic changes that play a role in energy metabolism, insulin response, and muscle inflammation

Increased blood flow from regular exercise adapts your brain to turn different genes on or off; many of these changes help protect against diseases such as Alzheimer’s and Parkinson’s

Virtually everyone would agree that exercise improves health, but the mechanisms by which it actually produces those benefits have been challenging to tease out.

Fitness research has come a long way though, and modern science has made a number of interesting observations that help explain how exercise affects your body to improve your health.

Part of the answer lies in its ability to affect genetic expression; activating some genes, and deactivating others. A previous New York Times article1 delved into the latest research on this front, noting that:

“The human genome is astonishingly complex and dynamic, with genes constantly turning on or off, depending on what biochemical signals they receive from the body. When genes are turned on, they express proteins that prompt physiological responses elsewhere in the body.”


The Epigenetics of Exercise

Far from being “written in stone,” genetic expression can be altered by influences coming from outside the gene. This influence alters the operation of the gene, but does not affect the DNA blueprint itself. This process is known as “epigenetics,” and occurs mainly through methylation. As described in the featured article:

“In methylation, clusters of atoms, called methyl groups, attach to the outside of a gene like microscopic mollusks and make the gene more or less able to receive and respond to biochemical signals from the body.”

Methylation patterns can be altered by a variety of lifestyle changes, such as diet and exercise. Toxic exposure also tends to affect genetic expression, by altering the types of proteins a particular gene will express.

In this way, your environment, diet, and general lifestyle play a significant role in your state of health and development of disease. When it comes to exercise, previous research has found that exercise can induce immediate changes in the methylation patterns of genes found in your muscle cells.

A study published in the journal Cell Metabolism2 in 2012 showed that while the underlying genetic code in the muscle remains unchanged, vigorous exercise—even if brief—causes structural and chemical changes in the DNA molecules within the muscles.

This gene activation is induced by contraction of the muscle, and this contraction-induced gene activation appears to be part of the chain of events that lead to the genetic reprogramming of muscle for strength—and to the structural and metabolic benefits of exercise.

Several of the genes affected by an acute bout of exercise are genes involved in fat metabolism. Specifically, the study suggests that when you exercise, your body almost immediately experiences genetic activation that increases the production of fat-busting proteins.

Previous studies have also identified and measured a wide variety of biochemical changes that occur during exercise. More than 20 different metabolites3 are affected, including compounds that help stabilize your blood sugar. All of these biochemical changes create a positive feedback loop, resulting in improved health and physical performance.


How Endurance Training Affects Your Genes

These kinds of findings led to another question: does endurance training (opposed to a brief intense bout of exercise) also affect methylation, and if so, how? A Swedish study4 published in December 2014 sought to shed light on this question.

As reported in the featured article:

“[S]cientists at the Karolinska Institute in Stockholm recruited 23 young and healthy men and women, brought them to the lab for a series of physical performance and medical tests, including a muscle biopsy, and then asked them to exercise half of their lower bodies for three months.

One of the obstacles in the past to precisely studying epigenetic changes has been that so many aspects of our lives affect our methylation patterns, making it difficult to isolate the effects of exercise from those of diet or other behaviors.

The Karolinska scientists overturned that obstacle by the simple expedient of having their volunteers bicycle using only one leg, leaving the other unexercised.

In effect, each person became his or her own control group. Both legs would undergo methylation patterns influenced by his or her entire life; but only the pedaling leg would show changes related to exercise.”

The volunteers performed their one-legged pedal exercise, at a moderate pace, for 45 minutes four times a week for three months. The result? The exercised leg was stronger than the unexercised leg, confirming that exercise led to physical improvement, as you would expect.

Genetic alterations within the cells of the muscles revealed there was more to the story however. More than 5,000 sites on the muscle cells’ genome, biopsied from the exercised leg, had altered methylation patterns. These changes were not found in biopsied cells from the unexercised leg. A majority of the methylation changes that occurred in the exercised leg play a role in:

  • Energy metabolism
  • Insulin response
  • Muscle inflammation

Endurance Training versus High Intensity Exercise

Quite clearly, exercise—in all its forms—tends to have a positive effect. It has the power to affect your entire body, and your overall state of health. Its beneficial impact on your insulin response (normalizing your glucose and insulin levels by optimizing insulin receptor sensitivity) is among the most important benefits of exercise, as insulin resistance is a factor in most chronic disease. According to lead author Malene Lindholm:5

“Through endurance training — a lifestyle change that is easily available for most people and doesn’t cost much money—we can induce changes that affect how we use our genes and, through that, get healthier and more functional muscles that ultimately improve our quality of life.”

High intensity interval training (HIIT) has been shown to be far more effective at producing positive results however, when compared to endurance training. And while the study above concluded that endurance training indeed induces genetic alterations that promote good health, HIIT is known to do so far more efficiently. Mounting research shows that by focusing on endurance-type exercises, such as jogging on a treadmill, you actually forgo many of the most profound benefits of exercise.

Some of the latest research in high intensity exercise involves myokines—a class of cell-signaling proteins produced by muscle fibers—and how they can combat diseases like metabolic syndrome and cancer. I interviewed Dr. Doug McGuff about this research last year. These myokines—which are cytokines produced in muscle—are very anti-inflammatory. They also increase your insulin sensitivity and your glucose utilization inside the muscle. High intensity strength training, also known as “super-slow strength training,” is likely the most effective in terms of activating myokines.

The reason for this is because it induces a rapid and deep level of muscle fatigue. This triggers the synthesis of more contractile tissue, and all the metabolic components to support it—including more myokines. If you still have not incorporated high intensity exercise into your fitness regimen, I highly recommend getting started. You can learn more about HIIT here,6 as there are many different programs to choose from. I also review the similarities and differences between super-slow and super-super-slow strength training techniques in this previous article.7

The Many Biological Effects of Exercise

Getting back to the effects of exercise in general, a number of biological effects occur when you work out. This includes changes in your:

  • Muscles, which use glucose and ATP for contraction and movement. To create more ATP, your body needs extra oxygen, so breathing increases and your heart starts pumping more blood to your muscles. Without sufficient oxygen, lactic acid will form instead. Tiny tears in your muscles make them grow bigger and stronger as they heal.
  • Lungs. As your muscles call for more oxygen (as much as 15 times more oxygen than when you’re at rest), your breathing rate increases. Once the muscles surrounding your lungs cannot move any faster, you’ve reached what’s called your VO2 max—your maximum capacity of oxygen use. The higher your VO2 max, the fitter you are.
  • Heart. As mentioned, your heart rate increases with physical activity to supply more oxygenated blood to your muscles. The fitter you are, the more efficiently your heart can do this, allowing you to work out longer and harder. As a side effect, this increased efficiency will also reduce your resting heart rate. Your blood pressure will also decrease as a result of new blood vessels forming.
  • Joints and bones, as exercise can place as much as five or six times more than your body weight on them. Peak bone mass is achieved in adulthood and then begins a slow decline, but exercise can help you to maintain healthy bone mass as you get older. Weight-bearing exercise is actually one of the most effective remedies against osteoporosis, as your bones are very porous and soft, and as you get older your bones can easily become less dense and hence, more brittle — especially if you are inactive.

Exercise Is Important for Optimal Brain Health, Too

Mounting research also shows that exercise is as important for your brain function as it is for the rest of your body. In fact, it may be part and parcel of staying “sharp as a tack” well into old age. For starters, the increased blood flow allows your brain to almost immediately function better. As a result, you tend to feel more focused after a workout.  More importantly though, exercising regularly will prompt the growth of new brain cells. In your hippocampus, these new brain cells help boost memory and learning.8 It also helps preserve both gray and white matter in your brain, which prevents cognitive deterioration that can occur with age.9,10

Genetic changes occur here, too. The increased blood flow adapts your brain to turn different genes on or off, and many of these changes help protect against diseases such as Alzheimer’s and Parkinson’s. A number of neurotransmitters are also triggered, such as endorphins, serotonin, dopamine, glutamate, and GABA. Some of these are well-known for their role in mood control. Not surprisingly, exercise is one of the most effective prevention and treatment strategies for depression. Three of the mechanisms by which exercise produces these beneficial changes in your brain are:

  • Increasing Brain Derived Neurotrophic Factor (BDNF). Exercise stimulates the production of a protein called FNDC5, which in turn triggers the production of BDNF, which has remarkable rejuvenating abilities. In your brain, BDNF both preserves existing brain cells,11 and activates brain stem cells to convert into new neurons, effectively making your brain grow larger.12
  • Decreasing BMP and boosting Noggin: Bone-morphogenetic protein (BMP) slows down the creation of new neurons, thereby reducing neurogenesis. If you have high levels of BMP, your brain grows slower and less nimble. Exercise reduces the impact of BMP, so that your adult stem cells can continue performing their vital functions of keeping your brain agile.In animal research,13,14 mice with access to running wheels reduced the BMP in their brains by half in just one week. In addition, they also had a notable increase in another brain protein called Noggin, which acts as a BMP antagonist. So, exercise not only reduces the detrimental effects of BMP, it simultaneously boosts the more beneficial Noggin as well. This complex interplay between BMP and Noggin appears to be yet another powerful factor that helps ensure the proliferation and youthfulness of your neurons.
  • Reducing plaque formation: By altering the way damaging proteins reside inside your brain, exercise may help slow the development of Alzheimer’s disease.15

Exercise Leverages Other Healthy Lifestyle Changes

While diet accounts for about 80 percent of the health benefits you get from a healthy lifestyle, exercise is the ultimate “leveraging agent” that kicks all those benefits up a notch. The earlier you begin and the more consistent you are, the greater your long-term rewards, but it’s never too late to start. Even seniors can improve their physical and mental health—not to mention physical function—by starting up an appropriate exercise program. Strength training is particularly important for the elderly, and super-slow strength training tends to be both safer and more effective than many other alternatives.

I believe that, overall, high-intensity interval training really helps maximize the health benefits of exercise, while simultaneously being the most efficient and therefore requiring the least amount of time. That said, ideally you’ll want to strive for a varied and well-rounded fitness program that incorporates a wide variety of exercises.

I also strongly recommend avoiding sitting as much as possible, and making it a point to walk more every day. A fitness tracker can be very helpful for this. I suggest aiming for 7,000 to 10,000 steps per day, in addition to your regular fitness regimen, not in lieu of it. The research is clearly showing that prolonged sitting is an independent risk factor for chronic disease and increases your mortality risk from all causes. So standing up more and engaging in non-exercise movement as much as possible is just as important for optimal health as having a regular fitness regimen.

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