Exercised: The Science of Physical Activity, Rest and Health

by Daniel E. Lieberman

Indeed, studies that try to figure out who does and doesn’t regularly exercise find few factors common to exercisers apart from some really obvious ones: having a prior history of exercising, being healthy and not overweight, having confidence in the ability to exercise, being more educated, and both liking and wanting to exercise.

Humans are intensely social creatures, and more than any other species we cooperate with unrelated strangers. We used to hunt and gather together, and we still share food, shelter, and other resources, we help raise one another’s children, we fight together, we play together. As a result, we have been selected to enjoy doing activities in groups, to assist one another, and to care what others think of us.15 Physical activities like exercise are no exception. When we struggle with fatigue or lack of skill, we encourage and help one another. When we succeed, we praise each other. And when we think of quitting, being in a group can deter us.

natural selection did adopt this drug-pushing strategy by having our brains manufacture an impressive cocktail of mood-altering pharmaceuticals in response to physical activity.16 The four most important of these endogenous drugs are dopamine, serotonin, endorphins, and endocannabinoids, but in a classic evolutionary design flaw these primarily reward people who are already physically active.

Endorphins. Endorphins are natural opioids that help us tolerate the discomfort of exertion.22 The body’s own opioids are less strong than heroin, codeine, and morphine, but they too blunt pain and produce feelings of euphoria. Opioids allow us to go for a long hike or run without noticing our muscles are sore and our feet have blisters. They may also contribute to exercise addiction.

Endocannabinoids. For years, endorphins were thought to cause the infamous runner’s high, but it is now evident that endocannabinoids—the body’s natural version of marijuana’s active ingredient—play a much greater role in this phenomenon.

not everyone has the genes that make a runner’s high possible.25 I suspect the runner’s high evolved primarily to increase sensory awareness to help hunters track animals during persistence hunting.

Commonly recommended, sensible methods to make exercise more fun (or less unfun) include: Be social: exercise with friends, a group, or a good, qualified trainer.27 Entertain yourself: listen to music, podcasts, or books, or watch a movie. Exercise outside in a beautiful environment. Dance or play sports and games. Because variety is enjoyable, experiment and mix things up. Choose realistic goals based on time, not performance, so you don’t set yourself up for disappointment. Reward yourself for exercising.

Because we never evolved to be inactive and out of shape, the adaptations that make physical activity feel rewarding and become a habit develop only after the several months of effort it takes to improve fitness. Slowly and gradually, exercise switches from being a negative feedback loop in which discomfort and lack of reward inhibit us from exercising again to being a positive feedback loop in which exercise becomes satisfying.

push weight machines. But of all the prescriptions, by far the most commonly and widely promoted—advocated by almost every major health organization in the world—is that we do at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic exercise per week, supplemented by two sessions of weights.

to reduce the overall risk of chronic disease, adults should engage in at least 30 minutes of moderate-intensity exercise at least five times a week.6 They also concluded that children should engage in 60 minutes of physical activity a day.

(Moderate-intensity aerobic activity is defined as between 50 and 70 percent of your maximum heart rate; vigorous-intensity aerobic activity is 70 to 85 percent of your maximum heart rate.)

Sustained increased cardiac output also stimulates the expansion of the many small arteries and capillaries where oxygen exchange occurs in muscles everywhere including the heart’s muscle itself. And aerobic exercise raises so-called good cholesterol (HDL) and lowers so-called bad cholesterol (LDL) and circulating fats (triglycerides).

In the eighteenth century it was fashionable to lift church bells that were silenced (made “dumb”) by having their clappers removed, hence the term “dumbbells.”

an evolutionary perspective makes the same commonsensical recommendations for physical activity that people have followed for centuries, albeit using different terminologies: exercise several hours a week, mostly cardio but also some weights, and keep it up as you age.

(BMI): weight (in kilograms) divided by height (in meters) squared.

by convention a BMI between 18.5 and 25.0 is considered normal, 25.0–30.0 is overweight, and above 30.0 is obese.

When we are in positive energy balance from consuming more calories than we expend, we convert surplus calories into fat that we store in fat cells. When we are in negative energy balance from spending more calories than we consume, we burn some of this fat. This calories-in-calories-out equation, however, is regulated by hormones, which in turn are strongly affected by diet and by other factors including psychosocial stress, the microbes in our gut, and, of course, physical activity.

Aside from overloading joints and interfering with breathing, excess fat cells overproduce hormones that alter metabolism, and when swollen, they become invaded by white blood cells that ignite chronic low-grade inflammation, damaging tissues throughout the body. Big deposits of enlarged fat cells in and around organs (so-called visceral, abdominal, or organ fat) are especially hazardous because they react sensitively to hormones and connect more directly to the bloodstream.

The English physician Thomas Willis (1621–1675) coined the term “diabetes mellitus” (Latin for “honey sweetened”), what we now call diabetes, from urine that was “wonderfully sweet as if it were imbued with honey or sugar.”

It bears repeating that too many swollen fat cells, especially in the liver and other organs, cause inflammation and high levels of triglycerides that provoke insulin resistance, which further worsens these problems. Bad diets promote obesity and deluge the bloodstream with sugar and fat. Stress elevates cortisol, which releases blood sugar, causes organ fat to accumulate, and facilitates inflammation. Last but not least, persistent sedentariness contributes to metabolic syndrome by elevating blood sugar and fat levels and failing to dampen inflammation.

exercise can reverse insulin resistance by restoring blocked insulin receptors and causing muscle cells to produce more of the transporter molecules that shuttle sugar out of the bloodstream.

A cholesterol test usually measures the levels of three molecules in your blood. The first is low-density lipoprotein (LDL), often termed bad cholesterol. Your liver produces these balloon-like molecules to transport fats and cholesterol throughout your bloodstream, but some LDLs have a harmful tendency to burrow into the walls of arteries, especially when blood pressure is high. These intrusions cause an inflammatory reaction that generates plaques. The second type of cholesterol is high-density lipoprotein (HDL), sometimes called good cholesterol, because these molecules scavenge and return LDLs back to the liver. The third type are triglycerides, fat molecules that are floating freely in the bloodstream and a signpost for metabolic syndrome.

physical activity helps prevent cardiovascular disease by lowering triglycerides, raising HDL levels, and to a lesser degree lowering LDL.

Plaques don’t form out of the blue but instead occur when white blood cells in the bloodstream react to the inflammation caused by LDLs and high blood pressure. Chronic inflammation also increases one’s likelihood of developing plaques from high cholesterol and blood pressure.

Age-related loss occurs in both men and women but is exacerbated in women after menopause, when there is a drop in levels of estrogen, which protects bones from being resorbed.

In particular, weight-bearing activities that load the skeleton cause bone-growing cells to add more bone when we are young, and they prevent bone-resorbing cells from removing bone as we age.

The most common cancers occur in reproductive organs, intestines, skin, lungs, and marrow because cells in these tissues divide frequently and are exposed to external influences like radiation, toxins, and hormones that affect their likelihood of dividing or mutating.

High levels of physical activity divert energy from cancerous cells in at least four possible ways.

Reproductive hormones. Energy spent on physical activity is energy not spent on reproduction, a trade-off modulated by reproductive hormones like estrogen. Women who exercise moderately produce more than enough hormones to reproduce, but the bodies of sedentary women naturally shunt more energy toward reproduction, leading to 25 percent higher levels of estrogen.95 Because reproductive hormones like estrogen induce cell division in breast tissue, inactivity increases the risk of breast cancer, while exercise has the opposite effect. Levels of estrogen, hence breast cancer, are also elevated by obesity and by having fewer pregnancies.

Sugar. Some cancer cells have a sweet tooth. In fact, many cancer cells tend to get their energy directly from sugars, which they burn anaerobically without oxygen. High levels of blood sugar from metabolic syndrome are thus associated with increased rates of cancer.97 Exercise may thus help prevent and fight cancer by depriving cancer cells of ready energy. Furthermore, because high-intensity exercise inhibits anaerobic sugar metabolism, extremely vigorous exercise may be especially effective for preventing and fighting certain cancers.

Inflammation. Inflammation, which goes hand in hand with chronic positive energy balance and obesity, is a risk factor for many cancers. As we have already seen, inflammation causes various kinds of cellular damage, some of which are associated with mutations that can lead to cancer.99 Physical activity thus counters cancer indirectly by helping prevent or reduce levels of inflammation either directly or indirectly.

Antioxidants and immune function. Physical activity stimulates the body to spend energy on repair and maintenance systems to mop up the damage that exercise might cause in the first place. One of these investments is antioxidant production. These cleanup molecules counteract highly reactive atoms that cause many kinds of damage including potentially cancerous mutations.100 In addition, non-extreme levels of exercise boost the immune system, which plays a vital role in fighting cancer. An especially promising discovery is that vigorous exercise potently enhances the effectiveness of natural killer (NK) cells, the immune system’s primary weapon that recognizes and destroys cancerous cells.

physical activity—especially of longer duration but also more vigorous activities—causes the brain to produce a powerful molecule known as BDNF (brain-derived neurotrophic factor). BDNF first evolved to help mammals get energy during physical activity and at some point took on additional roles in the brain.

because we never evolved to be persistently sedentary, we never evolved a mechanism other than physical activity to produce high levels of BDNF. In a classic mismatch, absence of exercise deprives us of doses of BDNF that have been shown to improve memory and cognition and to maintain neuronal health that apparently helps prevent Alzheimer’s.

Make exercise necessary and fun. Do mostly cardio, but also some weights. Some is better than none. Keep it up as you age.

For every liter of O2 you use, your body gets 5.1 kilocalories (kcals) from burning pure carbohydrates, and 4.7 kcal from burning pure fat. The ratio of O2/CO2 you expire signals how much fat versus carbohydrate you are using. If you are burning only carbohydrate, you produce exactly as much CO2 as O2, and if you are burning only fat, you produce 70 percent as much CO2 as O2. Most of the time, you burn a mixture of fat and carbohydrate, yielding an average of 4.8 kcal for every liter of oxygen.

Here is a more detailed explanation of the “doubly labeled water” method. Most water, H2O, is made from hydrogen with a molecular weight of 1 (1H, which has 1 proton) and oxygen with a molecular weight of 16 (16O, which has 8 protons and 8 neutrons). It is also possible to make a harmless form of water using “heavy” hydrogen (2H, which has an extra neutron) and oxygen (18O, which has two extra neutrons). Regardless of what kind of hydrogen and oxygen is in the water, the H and O leave the body in different ways: the H and O leave as water when we urinate, breathe, and sweat, whereas the O also leaves the body when we breathe out carbon dioxide (CO2). Because we can accurately and precisely measure 2H and 18O in urine, the difference in the rate at which H versus 18O remains in your urine over several days allows us to calculate how much CO2 you breathed out, thus allowing a reasonably precise calculation of how much energy you spent. The method also allows us to calculate your fat-free body mass and how much water goes in and out of your body.

Hadza men and women average 13 percent and 21 percent body fat, respectively; industrialized men and women average 23 percent and 38 percent body fat, respectively.

When humans who grew up in pathogen-rich conditions get an infection, their inflammatory response is sudden, strong, but short-lived. In contrast, the immune systems of people who grew up in highly hygienic environments with dishwashers, indoor plumbing, bleach, and lots of soap are different. When they get an infection, their inflammatory response tends to be much slower and less intense and lasts much longer.

The brain is bathed in cerebrospinal fluid that keeps blood away from brain cells. This is because direct contact with blood destroys neurons (as, for example, during a stroke). In addition, by keeping blood away from direct contact with the brain, the blood-brain barrier prevents infectious agents and toxins in the bloodstream from getting into the brain.

I’ve been focusing here on the energetic disadvantages of being bipedal, but being upright causes a host of other problems, one of which is that our heads jiggle dreadfully. A human runner’s head bounces up and down, but the head of a galloping dog or horse stays impressively still even though the rest of its body is moving. The quadruped’s head looks like a missile mounted on its body. This missile-like stability is crucial for running because the reflexes that stabilize the eyeballs to keep an animal’s vision from blurring are not fast enough to overcome rapid displacements. Experiments show that when the head rotates too fast, animals (including humans) can no longer effectively focus on whatever they are looking at including obstacles in their way. Overly bouncy heads are thus potentially perilous for runners. Quadrupeds solve this problem by having a relatively horizontal neck that runs from the front of the thorax to the back of the head. Thanks to this cantilevered configuration, when the animal’s body falls or rises, it raises or lowers its neck to keep its head still. Some animals have gone a step further and added a highly elastic structure (the nuchal ligament) that passively stabilizes the head without requiring muscles to do much work. Humans, however, run like pogo sticks because we have short, little, vertical necks that attach to the middle of the base of the skull. Although we have evolved some special mechanisms to keep our heads from pitching too much, t...

We can also break down protein as a source of fuel, but this is much less common and occurs only when fat and sugars are in short supply. Also, in case you were wondering, ADP sometimes can be broken down to an AMP (adenosine monophosphate), releasing yet more energy. This happens less often, though.

glycolysis is a ten-step process that requires two ATPs per sugar, yielding four ATPs, hence a net of two ATPs.

Interestingly, no ATP is required for a myosin head to bind to an actin protein, but ATP causes each myosin head to ratchet and then release itself from the actin. As a result, when ATP runs out after death, muscles go into rigor mortis in the absence of ATP to release the myosin heads from the actin.

In terms of absolute time, humans start walking later than most animals, but the delay has nothing to do with the fact that we walk on two versus four legs. With the exception of highly vulnerable quadrupeds like zebras, which risk being eaten by hyenas and lions and can walk within a day of birth, the age at which most animals start walking is primarily determined by how far along the brain has finished developing. Primates like macaques with smaller brains start walking at two months, bigger-brained chimpanzee infants require about six months to start walking, and humans start walking just at the age, one year, predicted by our brain development.

The notion behind fat-burning zones is that the harder you work, the more energy you burn, but a greater proportion of that energy is carbohydrate (glycogen). When sitting quietly, you burn only fat but not much. When you walk, jog, run, and then sprint, you burn more energy, but with greater intensity a higher percentage is glycogen, so at maximum capacity you burn only glycogen. The fat-burning zone is thus a low-to-moderate level of activity that burns about as much fat as glycogen, but it’s sort of a fiction because there is a wide range of variation between individuals of moderate activity levels in which you may burn a lower percentage of but maximum amount of fat.

All your cells have the same genome, so you need epigenetic modifications to enable a skin cell to function differently from a neuron or a muscle cell. Some epigenetic modifications appear to be passed on from one generation to the next, making this a nongenetic form of inheritance.

In a phenomenon known as antagonistic pleiotropy (“pleiotropy” is the technical term for a gene that has multiple effects), a gene that helps us survive and reproduce when we are young might turn out to be harmful when we get older. One infamously extreme example is a mutation that improves immune function earlier in life but causes Huntington’s disease (a fatal form of brain degeneration) in middle age.

The tendency to postpone long-term benefits for short-term alternatives is known as temporal discounting. Economists and psychologists have shown this is a common behavior that leads people to make irrational decisions.