Exercised: The Science of Physical Activity, Rest and Health

by Daniel E. Lieberman

In fact, when researchers first started to study myokines, they were astonished to discover that muscles regulate inflammation during bouts of moderate to intense physical activity similarly to the way the immune system mounts an inflammatory response to an infection or a wound.40

Without going into too many details, we have learned that the body first initiates a proactive inflammatory response to moderate- or high-intensity physical activity to prevent or repair damage caused by the physiological stress of exercise and subsequently activates a second, larger anti-inflammatory response to return us to a non-inflamed state.

In fact, none of the mechanisms that inflame us—swollen fat cells, too much fat and sugar in the bloodstream, stress, and inactive muscles—are caused by sitting per se. Instead, they result from the absence of being sufficiently physically active, which usually means a lot of sitting.

Because you and I may sit the same number of hours but in different ways and contexts, we need to consider how different patterns of sitting—extended versus interrupted—potentially affect chronic, low-grade inflammation.

An even larger study based on survey data from more than 240,000 Americans found that time engaged in moderate and vigorous activity lowered but did not erase the risk of dying associated with being sedentary.46 Even those who engaged in more than seven hours per week of moderate or vigorous exercise had a 50 percent higher risk of dying from cardiovascular disease if they otherwise sat a lot.

Altogether, these and other alarming studies suggest that even if you are physically active and fit, the more time you spend sitting in a chair, the higher your risk of chronic illnesses linked to inflammation, including some forms of cancer.

In fact, people who rarely sat for more than twelve minutes at a time had lower death rates, and those who tended to sit for half an hour or longer at a stretch without getting up had especially high death rates.

When I sat down to read these papers, I was frankly astonished: nearly all high-quality studies on this topic fail to find consistent evidence linking habitual sitting in flexed or slouched postures with back pain.68 I was also surprised to read there is no good evidence that people who sit longer are more likely to have back pain,69 or that we can lessen the incidence of back pain by using special chairs or getting up frequently.70 Instead, the best predictor of avoiding back pain is having a strong lower back with muscles that are more resistant to fatigue; in turn, people with strong, fatigue-resistant backs are more likely to have better posture.

Instead of vilifying chairs and remonstrating yourself for slouching or not squatting, try to find ways to sit more actively without being inert for too long, squirm shamelessly, and don’t let sitting get in the way of also exercising or otherwise being physically active. Such habits prevent or lessen chronic inflammation that provokes ill health, and it bears repeating that the scary statistics we read about sitting are primarily driven by how much we sit when not at work.

During sleep, our metabolic rate drops about 10 to 15 percent; about 80 percent of growth also occurs during NREM sleep.

One conspicuous benefit is cognitive: sleep helps us remember important things and helps synthesize and integrate them.

Effective cognition, however, requires organisms to sort through all the memories they generate every day, throw out the inconsequential ones, store the important ones, and make sense of them.

As the day marches on, we store memories in a region of the brain called the hippocampus, which functions as a short-term storage center like a USB drive. Then, during NREM sleep, the brain triages these memories, rejecting the innumerable useless ones (like what color socks the man sitting next to me on the subway wore) and sending the important ones to long-term storage centers near the surface of the brain.

And, fantastically, the brain may also analyze certain memories during REM sleep, integrating them and looking for patterns. Critically, however, the brain has limited abilities to multitask and cannot perform these cleaning, organizing, and analytical functions as effectively when we are awake and alert.

An even more vital function of sleep for the brain is janitorial. The zillions of chemical reactions that make life possible inevitably create waste products known as metabolites, some highly reactive and damaging.12 Because the power-hungry brain uses one-fifth of the body’s calories, it generates abundant and highly concentrated metabolites. Some of these garbagy molecules such as beta-amyloid clog up neurons.13 Others such as adenosine make us sleepy as they accumulate (and are counteracted by caffeine).14 Getting rid of these waste products, however, is a challenge.

Whereas tissues like liver and muscle wash out metabolites directly into blood, the brain is tightly sealed off from the circulatory system by a blood-brain barrier that prevents blood from coming into direct contact with brain cells.15

To rid itself of waste, the brain evolved a novel plumbing system that relies on sleep. During NREM sleep, specialized cells throughout the brain expand the spaces between neurons by as much as 60 percent, allowing cerebrospinal fl...

Sleep is therefore a necessary trade-off that improves brain function at the cost of time. For every hour spent awake storing memories and amassing waste, we need approximately fifteen minutes asleep to process those memories and clean up.

One novelty of the modern world is our tendency to medicalize certain behaviors by prescribing them in specific doses.

So if you sometimes wake up in the middle of the night or sleep seven rather than eight hours a night, relax.

As we go through the initial stages of NREM sleep, we become gradually less aware of our environment. This progressive tuning out may be adaptive because our brain is monitoring the world around us as we fall asleep, possibly to assess whether it is dangerous to sleep. Slowly receding perceptions of nearby friends and family talking, a crackling fire, infants crying, and the fact that those hyenas are far away signal to the brain that it is safe to enter a deeper, unconscious stage of sleep.

Why do so many people excel at resting too much during the day but then fail to rest enough at night? To answer this question, we need to consider the two major biological processes that interact in the brain to regulate wakefulness and sleep.51 When these processes function normally, we wake up in the morning feeling refreshed, stay pleasantly alert for most of the day, and then fall gently asleep at night.

The first system is our nearly twenty-four-hour circadian cycle regulated by a specialized group of cells within a region of the brain known as the hypothalamus.

These cells wake us up in the morning by signaling to the glands atop our kidneys to produce cortisol, the major hormone that stimulates the body to spend energy.

Then as darkness falls, the hypothalamus directs the pineal gland, another structure in the brain, to produce melatonin, the “Dracula hormone,” which helps induce sleep.

This homeostatic system functions like an hourglass that counts how long we’ve been awake, slowly building up pressure for us to sleep. The longer we stay awake, the more sleep pressure we accrue from the accumulation of molecules such as adenosine left behind when the brain expends energy. Then by sleeping, we reset the hourglass, primarily through NREM sleep. Overall, the homeostatic system helps balance the time we spend awake versus asleep, and if we are up too long, it will eventually override our circadian systems and help us recover lost sleeping time.

The effects of the fight-and-flight response (technically, the sympathetic nervous system) on sleep explain how and why exercise has such important, well-known effects on sleep. If you run a mile at top speed or lift heavy weights just before going to bed, you’ll probably have a hard time falling asleep because vigorous physical activity turns on this system, stimulating arousal. In contrast, a good dose of physical activity earlier in the day like a game of soccer, an hour or two of gardening, or a long walk helps sleep come more easily.

Among other benefits, recovery from exercise gradually lowers basal cortisol and epinephrine levels, depresses body temperature, and even helps re-sync the circadian clock.

One survey of more than twenty-six hundred Americans of all ages that controlled for factors like weight, age, health status, smoking, and depression found that those who regularly engaged in at least 150 minutes of moderate to vigorous activity a week not only reported a 65 percent improvement in sleep quality but also were less likely to feel overly sleepy during the day.

To quote Jerome Siegel, “In twenty years, people will look back on the sleeping-pill era as we now look back on the acceptance of cigarette smoking.”

It bears repeating that sleep and physical activity are inextricably linked: the more physically active we are, the better we sleep because physical activity builds up sleep pressure and reduces chronic stress, hence insomnia. In that sense, physical activity and sleep are not trade-offs but collaborators.

Because speed is the product of stride length and stride rate (a stride being a full cycle from the time a foot hits the ground to the next time the same foot hits the ground), one can go faster by taking longer strides, by taking more rapid strides, or some combination of the two.

However, for Bolt to drive his legs that fast required incredible strength.

The problem is, however, that regardless of whether we are hyenas or humans, the faster we run, the more our bodies struggle to recharge these ATPs, thus curtailing our speed after a short while.

You use more than thirty pounds of ATP during a one-hour walk and more than your entire body weight of ATP over the course of a typical day—an obviously impossible amount to lug around in reserve.

Sugar is synonymous with sweetness, but it’s first and foremost a fuel used to recharge ATPs through a process termed glycolysis (from glyco for “sugar” and lysis for “break down”).

But there is a consequential catch: during glycolysis the leftover halves of each sugar, molecules known as pyruvates, accumulate faster than cells can handle. As pyruvates pile up to intolerable levels, enzymes convert each pyruvate into a molecule called lactate along with a hydrogen ion (H+). Although lactate is harmless and eventually used to recharge ATPs, those hydrogen ions make muscle cells increasingly acidic, causing fatigue, pain, and decreased function.

At first, the energy comes nearly instantly from stored ATP and creatine phosphate (CrP); later, energy comes relatively rapidly from glycolysis; eventually, energy must come from slowly aerobic metabolism. Aerobic metabolism occurs in mitochondria by liberating energy either from pyruvate (an end product of glycolysis) or fatty acids.

That’s because everyone’s aerobic system kicks in when they start exercising, but the maximum level of energy obtained this way varies highly from person to person. This important limit, illustrated in figure 12, is termed maximal oxygen uptake, or VO2 max.

As the treadmill goes faster and faster, you use more and more oxygen until your ability to use any additional oxygen plateaus and you start to gasp. At this limit, your VO2 max, you need glycolysis to supply additional fuel to your muscles.

Even if you are scrawny like me, your muscles make up a little over a third of your weight and consume roughly one-fifth of your daily calories.

Many of your muscles have a roughly fifty-fifty mixture of slow- and fast-twitch fibers, but the muscles you use mostly for generating power like your triceps are about 70 percent fast-twitch fibers, and those you use primarily for walking or other non-forceful activities like the deep muscles of your calf (the soleus) are roughly 85 percent slow-twitch fibers.29

Thousands of additional biopsies from an assortment of muscles have since confirmed these results: most of us have slightly more slow-than fast-twitch fibers, but athletes who excel at speed and power sports like Usain Bolt are dominated by fast-twitch fibers, and those who specialize in endurance sports such as the legendary marathoner Frank Shorter tend to have a preponderance of slow-twitch fibers.

Heritability estimates of speed range from 30 to 90 percent, and those of aerobic capacity range from 40 to 70 percent.35 These two- to threefold differences in heritability estimates are a valuable reminder that individual studies typically fail to capture the messy complexity of the real world.

So far, the best candidate gene associated with athletic talent goes by the insipid name of ACTN3. This gene codes for a protein that helps muscles remain stiff under high forces. Crucially, it has two different versions: a normal R, and a mutant X, which functions poorly, thus causing the muscle to be more elastic.

A highly publicized 2003 study of Australian athletes found that the X version of ACTN3 was common among nonathletes and endurance athletes but was almost nonexistent among elite sprinters, weight lifters, and other athletes whose sports require lots of force and power.37 This discovery caused some parents to pay geneticists to test their children to determine what kinds of sports they should encourage.

One study of Greek sprinters showed the gene explained at best 2.3 percent of the variation in forty-meter sprinting times,38 and other studies have found the gene has no predictive value at all among Africans and other non-Europeans.39

To make matters worse, despite explaining very little, ACTN3 is the most potent of the more than two hundred genes so far associated with athletic performance.

For those of us who think we are better suited for endurance than extreme speed, abundant evidence shows that occasional, regular bouts of high-intensity exercise make us not only stronger and faster but also fitter and healthier. This form of training, known as high-intensity interval training (HIIT), involves alternating short bouts of intense anaerobic exercise such as sprinting with less intense periods of recovery.

Although HIIT cannot stimulate your body to produce more fast-twitch muscle fibers, the ones you have will thicken, making you stronger and hence faster.