Exercised: Why Something We Never Evolved to Do Is Healthy and Rewarding

by Daniel E. Lieberman

Short bursts of intense cardio elevate heart rate and oxygen consumption close to their upper limit, usually above 85 or 90 percent of maximum rate. Athletes have long known that repeated surges of this intensity, termed high-intensity interval training, are an effective way to improve performance. HIIT usually involves short bouts, anywhere from ten to sixty seconds, of maximum effort that leaves one breathless (but not dangerously so) interspersed with periods of rest.

Because HIIT stresses the cardiovascular system more acutely than moderate-intensity aerobic exercise, it can yield rapid, dramatic benefits. Done properly, HIIT can substantially elevate aerobic and anaerobic fitness, bring down blood pressure, lower harmful cholesterol levels, burn fat, improve muscle function, and stimulate the production of growth factors that help protect the brain (more on this in chapter 13).38

when working against substantial loads, muscles can shorten (concentric contractions), but they are more stressed and grow larger and stronger in response to forceful contractions in which they stay the same length (isometric contractions) or stretch (eccentric contractions).

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.” Today’s gyms are stocked with an assortment of dumbbells, free weights, and contraptions that can be adjusted to place a constant level of resistance on muscles throughout their entire range of motion.

resistance activities are critical for maintaining muscle mass, especially fast-twitch fibers that generate strength and power. Resistance exercise can also help prevent bone loss, augment muscles’ ability to use sugar, enhance some metabolic functions, and improve cholesterol levels. As a result, every major medical health organization recommends we supplement cardio with weights, especially as we age. A consensus suggestion is two sessions per week of muscle-strengthening exercises involving all major muscle groups (legs, hips, back, core, shoulders, and arms). Space these sessions several days apart to permit recovery, and they needn’t involve large weights but should include eight to twelve repetitions of each exercise tiring enough to make you want to stop; two or three sets of exercises are more effective than just one.

As we age, daily hours of minimal physical activity—typically in chairs—render us more vulnerable to a litany of chronic illnesses and disabilities that used to be rare or unknown such as heart disease, hypertension, many cancers, osteoporosis, osteoarthritis, and Alzheimer’s. It is commonly assumed that these conditions are the inevitable by-products of more of us living to be older. But this is not entirely true. Exercise may not be an elixir, but by stimulating growth, maintenance, and repair, it can reduce our susceptibility to many of these mismatches. In this sense, exercise is medicinal. And unlike other medicines, exercise is free, has no side effects, and is sometimes fun. So to stay healthy and fit, many of us exercise.

If mismatches are caused by harmful interactions between genes and environments in which environments rather than genes recently changed, it’s hard to find a bigger example than obesity. Although some of us carry genes that make us more likely to become obese, the role of environment is uncontested. Obesity is almost unknown among foraging populations and was much less common a few generations ago, but nearly two billion people are now overweight or 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.

Disgusting as that may sound, if you were a doctor back in the old days, you’d be a pee connoisseur. As a matter of routine, you would collect your patients’ “liquid gold” to examine its taste, color, smell, and consistency. Much of what doctors discerned from urine was nonsense, but an exception was its sweetness. 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.”14

Although too much sugar in your urine or blood is a sign of type 2 diabetes, the disease’s root cause is a problem termed insulin resistance. Imagine you just wolfed down a dozen cookies. As the sugar from the cookies floods your bloodstream, blood sugar levels rise. Because too much sugar is toxic to many cells, excess sugar stimulates your pancreas to release the hormone insulin, whose

basic function is to cause the body to store energy. Among its many actions, insulin directs special molecules on the surfaces of fat and muscle cells to transport sugar from the bloodstream into those cells to be stored or burned. Type 2 diabetes arises when the effects of metabolic syndrome prevent insulin receptors on these cells from binding with insulin (a phenomenon termed resistance). A vicious cycle ensues. When insulin binding doesn’t happen, the glucose transporters don’t take up sugar from the bloodstream. Then, as blood sugar levels rise, the brain desperately commands the pancreas to produce yet more insulin, but with diminishing effect, causing blood sugar levels to stay dangerously high. Symptoms include frequent thirst and peeing, nausea, tingly skin, and swollen feet. Eventually, the overworked pancreas fails, requiring injections of insulin to avoid death.

The heart is essentially a muscular pump connected to an elaborate network of branching tubes. Although there are several kinds of cardiovascular disease, almost all arise from something going wrong in either the tubes or the pump. Most problems start with the tubes, primarily the arteries that carry blood from the heart to every nook and cranny of the body. Like the pipes in a building, arteries are vulnerable to getting clogged with unwanted deposits. This hardening of the arteries, termed atherosclerosis, starts with the buildup of plaque—a gloppy mixture of fat, cholesterol, and calcium—within the walls of arteries. Plaques, however, don’t simply accumulate in arteries like crud settling in a pipe. Instead, they are dynamic, changing, growing, shifting, and sometimes breaking. They develop when white blood cells in arteries trigger inflammation by reacting to damage usually caused by a combination of high blood pressure and so-called bad cholesterol that irritates the walls of the artery. In an effort to repair the damage, white blood cells produce a foamy mixture that incorporates cholesterol and other stuff and then hardens. As plaque accumulates, arteries stiffen and narrow, sometimes preventing enough blood from flowing to the tissues and organs that need it and further driving up blood pressure. One potentially lethal scenario is when plaques

block an artery completely or detach and obstruct a smaller artery elsewhere. When this happens, tissues are starved of blood (also called ischemia) and die. Plaques can also cause the artery wall to dilate, weaken, and bulge (an aneurysm) or to tear apart (a rupture), which can lead to massive bleeding (a hemorrhage).

Hypertension is a silent condition that relentlessly strains the heart, arteries, and various organs. At least 100,000 times a day, the heart forces about five liters of blood through thousands of miles of arteries that resist each squeeze, generating pressure. When we exercise, blood pressure rises temporarily, causing the heart’s muscular chambers to adapt, mostly by becoming stronger, larger, and more elastic so it can pump more blood with each stroke.30 Just as important, arteries also adapt to exercise to keep blood pressure low, primarily by expanding, multiplying, and staying elastic.31 However, when blood pressure is chronically high, the heart defends itself by developing thicker muscular walls. These thicker walls stiffen and fill with scar tissue, and eventually the heart weakens. A vicious cycle then ensues. As the heart’s ability to pump blood declines, it becomes harder to exercise and thus control high blood pressure. Blood pressure may rise as the heart progressively weakens until the failing heart cannot support or sustain a normal blood pressure. Death usually ensues.

Cholesterol. 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. To make a long story short, diets rich in sugar and saturated fats contribute to cardiovascular disease because they promote high levels of plaque-forming LDLs. Conversely, physical activity helps prevent cardiovascular disease by lowering triglycerides, raising HDL levels, and to a lesser degree lowering LDL.

Inflammation. 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.40 And, as we have previously seen, while inflammation is caused by factors such as obesity, junky diets, excess alcohol, and smoking, it is substantially lowered by physical activity.

While cardio unquestionably invigorates and strengthens the cardiovascular system, lifting weights also improves cholesterol levels (raising HDLs and lowering LDLs) and lowers resting blood pressure (although not as much as cardio).45 That said, doing only weights is apparently less protective than only cardio for the cardiovascular system.

Just as viruses, bacteria, and other pathogens are constantly evolving to invade our bodies, evade our immune systems, and make more copies of themselves that we then sneeze, cough, or otherwise disperse to infect others, our immune systems have been simultaneously evolving to fight back. This evolutionary arms race has been going on for hundreds of millions of years, but ever since the origins of agriculture, humans have made ourselves vastly more vulnerable to contagious diseases like cholera, smallpox, and RTIs that are passed from one person to another. Hunter-gatherers live in small groups at low population densities and in temporary camps with no farm animals,

but the development of agriculture and then industrialization enabled people to live permanently in villages, towns, and cities at extremely high population densities, often cheek by jowl with farm animals and other species like rats and mice. To make matters worse, sewers and clean water supplies were not constructed in most towns and cities until relatively recently, and public sanitation is still inadequate in many parts of the world. Contagious pathogens flourish in crowded, unhygienic conditions, and when they jump to humans from other species, they are especially dangerous because no one’s immune system has encountered them before. So, while hunter-gatherers suffer from plenty of infectious illnesses, highly contagious epidemic diseases like COVID-19 are partly mismatches made possible by civilization, and that explains why social distancing and handwashing are key tools to fight them.49

because heading off to the bush to hunt and gather potentially made our ancestors more likely to encounter pathogens, our immune systems evolved to compensate by ramping up our defenses when we are active. A related possible explanation stems from the stingy way our bodies use calories. The fatigue we experience when fighting a cold is a reminder that the immune system is often energetically costly. As a result, maybe our immune systems evolved to be less vigilant when they are less needed. For hunter-gatherers, unlike most industrial people, those times might have been when they were less physically active and thus less likely to be exposed to pathogens.

osteoarthritis has been around for millions of years (even some Neanderthals were afflicted) but our chances of getting this disease at a given age have more than doubled since World War II.71 Today, more than 25 percent of the U.S. adult population has been diagnosed with some form of osteoarthritis, most commonly in the knee.72 As always, the genes we inherited affect our susceptibility to sarcopenia, osteoporosis, and osteoarthritis. But because our genes haven’t changed over the last few generations, the chief culprit of these mismatches must be environmental change. Modern processed diets and obesity are major causes, but given the basic functions of muscles and bones it is hardly surprising that physical inactivity is also to blame.

Sarcopenia is the most obvious beneficiary of exercise. Because muscles are costly (right now, you are spending about one out of five calories simply maintaining your muscles73), they are the classic example of the “Use It or Lose It” principle of energy allocation. When we demand more from our muscles, especially contractions involving resistance, we activate genes that increase the size of fibers as well as repair and maintain muscle cells. As soon as we stop using them, muscles dwindle. Thus although aging affects hormone levels and nerve properties that inexorably diminish strength, staying physically active counters these declines.

Muscles benefit from all physical activities, but they respond most strongly to weight-bearing activities that require them to contract forcefully without changing length (isometric contractions) or as they lengthen (eccentric contractions). To prevent sarcopenia, do weights.

Cancer isn’t a single disease. Instead, it’s an umbrella term

for what happens when cells compete with each other in a kind of twisted unnatural selection within the body.86 Think of your body as a giant ecosystem with nearly forty trillion cells from more than two hundred different cell lines. Normally, these cells cooperate harmoniously even as they acquire random mutations, nearly all harmless. Every once in a while, however, cells develop mutations that disrupt their function, and a tiny fraction of those mutations trigger cells to compete with each other. When such mutations occur, the cells become malignant. At this point, they divide uncontrollably, migrate throughout the body, and voraciously consume calories. If your immune system fails to kill these cancerous cells quickly enough, they overtake organs, disrupt their function, and starve other cells. 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.

Alzheimer’s may thus be an example of an evolutionary phenomenon called the hygiene hypothesis. According to this idea, ApoE4, which can be expressed by cells in the brain, might have evolved long ago to help protect the brain when infectious diseases were ubiquitous. Those of us today who live in bizarrely sterile environments without many germs and worms, face an increased chance that these formerly protective immune mechanisms turn against us. (The hygiene hypothesis also helps explain increased rates of allergies and many other autoimmune diseases.109)

in understanding depression and anxiety disorders, but as articulated by Randolph Nesse and others, an evolutionary perspective that considers these diseases as adaptations gone awry may help explain why we are so vulnerable and why they are so varied.124 It is obviously adaptive for fear to lead us to avoid threats like poisonous snakes or being attacked by strangers. In anxiety disorder, however, these normal anxieties become irrational and uncontrolled. Likewise, it may sometimes be adaptive to be discouraged and unmotivated, hence disinclined to engage in behaviors unlikely to be successful like fighting someone who might kill us or wooing a lover who spurns us. In depression disorder, however, these low moods become directed persistently at ourselves, not the outside world. Just how and why these sorts of adaptive mechanisms turn pathological is poorly understood. As with all diseases, they involve interactions between genes and many complex environmental factors. But an evolutionary perspective prompts us to scrutinize the crucial role of the environment: Could these too be mismatch diseases? Are we vulnerable because we now face environmental factors, requiring less physical activity, that we never evolved to handle?

familiar. First, physical activity has many direct effects on the brain. One is to flood the brain with mood-altering chemicals. As a reminder, exercise heightens the activity of transmitting molecules in the brain, notably dopamine, serotonin, and norepinephrine.131 These neurotransmitters induce sensations of reward, well-being, arousal, and memory enhancement. Most pharmaceuticals such as SSRIs used to treat depression and anxiety manipulate levels of these neurotransmitters. Exercise also increases levels of other neurotransmitters, glutamate and GABA, that are often depleted in people with depression and anxiety.132 Additional mood-enhancing molecules turned on by exercise include endogenous opioids such as endorphins and endocannabinoids that inhibit pain and produce positive moods.133 Finally, as if this were not enough, remember that physical activity increases levels of BDNF and other growth factors that help maintain brain function. Altogether, regular physical activity alters brain chemistry, enhances electrical activity, and improves brain structure. Among other differences, the brains of more physically active people have enlarged memory regions, more cells, and increased blood supply.134 These evolutionarily normal characteristics may reduce vulnerability to disease.

philosophy for how to use one’s body is just as useful as a philosophy for how to live one’s life. All of us get only one chance to enjoy a good life, and we don’t want to die full of regret for having mislived it, and that includes having misused one’s body. By following deep and ancient instincts to avoid the discomfort that comes with physical exertion, we increase the chances we will senesce faster and die younger, and we become more vulnerable to many diseases and chronic, disabling

illnesses. We also miss out on the vigor, both physical and mental, that comes from being fit. To be sure, exercise is no magic pill that guarantees good health and a long life, and it is possible to live a reasonably long and healthy life without exercising. But thanks to our evolutionary history, lifelong physical activity dramatically increases the chances we will die healthy after seven or more decades.