The New Science of Exercise

Ever since high school, Dr. Mark Tarnopolsky has blurred the line between jock and nerd. After working out every morning and doing 200 push-ups, he runs three miles to his lab at McMaster University in Ontario. When he was younger, Tarnopolsky dreamed of becoming a gym teacher. But now, in his backup career as a genetic metabolic neurologist, he’s determined to prove that exercise can be used as medicine for even the sickest patients.

“People would always say to me, ‘Exercise? Come on. Scientifically, you can’t come up with a mechanism, so it’s a complete waste of time,'” Tarnopolsky says. “But as time goes on, paper after paper after paper shows that the most effective, potent way that we can improve quality of life and duration of life is exercise.”

Tarnopolsky has published some of those papers himself. In 2011, he and a team studied mice with a terrible genetic disease that caused them to age prematurely. Over the course of five months, half of the mice were sedentary. The other half were coaxed to run three times a week on a miniature treadmill.

By the end of the study, the sedentary mice were barely hanging on. The fur that had yet to fall out had grown coarse and gray, muscles shriveled, hearts weakened, skin thinned–even the mice’s hearing got worse. “They were shivering in the corner, about to die,” Tarnopolsky says.

But the group of mice that exercised, genetically compromised though they were, were nearly indistinguishable from healthy mice. Their coats were sleek and black, they ran around their cages, they could even reproduce. “We almost completely prevented the premature aging in the animals,” Tarnopolsky says.

That’s remarkable news, if you’re a mouse. And though there are obvious differences between rodents and humans, Tarnopolsky has seen something similar happen in his ill patients. “I’ve seen all the hype about gene therapy for people with genetic disease”–Tarnopolsky treats kids with severe genetic diseases like muscular dystrophy–“but it hasn’t delivered in the 25 years I’ve been doing this,” he says. “The most effective therapy available to my patients right now is exercise.”

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Tarnopolsky now thinks he knows why. In studies where blood is drawn immediately after people exercised, researchers have found that many positive changes occur throughout the body during and right after a workout. “Going for a run is going to improve your skin health, your eye health, your gonadal health,” he says. “It’s unbelievable.” If there were a drug that could do for human health everything that exercise can, it would likely be the most valuable pharmaceutical ever developed.

The trouble is only 20% of Americans get the recommended 150 minutes of strength and cardiovascular physical activity per week, more than half of all baby boomers report doing no exercise whatsoever, and 80.2 million Americans over age 6 are entirely inactive.

The consequences of a sedentary life are as well documented as they are dire. People with low levels of physical activity are at higher risk for many different kinds of cancer, heart disease, Alzheimer’s disease and early death by any cause. That’s at the end of life. Long before that, inactivity can worsen arthritis symptoms, increase lower-back pain and lead to depression and anxiety–not to mention cause a sallow complexion.

Despite public-awareness campaigns, the health benefits of exercise have not been effectively communicated to the average American. Humans are notoriously bad at assessing the long-term benefits–and risks–of their lifestyle choices. And vague promises that exercise is “good for you” or even “good for the heart” aren’t powerful enough to motivate most people to do something they think of as a chore. Humans are, however, motivated by rewards. That is why experts like Tarnopolsky are so focused on proving that the scientific benefits of exercise–slower aging, better mood, less chronic pain, stronger vision, the list goes on–are real, measurable and almost immediate.

The U.S. National Institutes of Health (NIH) is on the bandwagon too. Next year the agency will launch a massive new study with the aim of documenting in unprecedented detail exactly what happens inside a body in motion. Its hope: to prove that exercise is medicine.

Before doctors adopted a single-minded focus on treating and curing diseases, their main goal was to keep people healthy. Even back in 400 B.C., doctors knew that diet and exercise were the best ways to do that. “Eating alone will not keep a man well,” Hippocrates famously wrote. “He must also take exercise.” For millennia, doctors were the vanguards of physical education–the original PE teachers.

But in the early 1900s, with the rise of modern surgery and nascent pharmaceuticals, medicine shifted its focus from the prevention of disease to its treatment. Paradoxically, physicians de-emphasized exercise just as the modern Olympics swelled in popularity and colleges began building campus stadiums to accommodate America’s growing love of spectator sports. The authors of a paper published in a 1905 issue of the Journal of the American Medical Association mourned how many people were losing sight of the health benefits of exercise. “The men on the teams are the very ones whom Nature has endowed superabundantly with physical capacity, but on them the physical director bends most of his energies,” they wrote, “while the average student is left to get his physical development by yelling from the bleachers.”

Physical activity was no longer the medicine of the masses but the privilege of elite athletes. When scientists studied exercise, it was to figure out how athletes could improve their peak performance–not how mere mortals could improve their health day to day. This gap persists. At a time when boutique (read: expensive) fitness studios are more popular than ever, fewer people are getting the minimum recommended amount of exercise.

Worse, many U.S. schools have seen gym classes cut from the curriculum; nearly half of high school students don’t have weekly PE class, and only 15% of elementary schools require PE at least three days a week for the school year. The result: the majority of American kids and adolescents have so-called exercise-deficit disorder. Meanwhile, childhood-obesity rates have climbed every year since 1999. “You have whole generations that are soured on exercise,” says Jack Berryman, professor emeritus of medical history at the University of Washington School of Medicine.

Researchers like Tarnopolsky and Marcas Bamman, an exercise physiologist who also wants to be part of the NIH study, are hoping that their work will begin reversing those trends. Next year the NIH will launch its six-year, $170 million study with a group of about 3,000 sedentary people, ranging in age from children to the elderly. They will start an exercise program and then donate blood, fat and muscle before and after they exercise. Scientists will then examine samples for clues to how the body changes with physical activity. A control group that doesn’t exercise will also be tracked for comparison.

As part of the study, researchers will do the same experiment in animals to get tissue samples from places like the brain and the lungs that would be too dangerous to obtain from humans. “It’ll be a tremendously enormous data set,” says Maren Laughlin, program director for integrative metabolism at the NIH, who is also a lead on the new study. In the end, the researchers think they’ll be able to identify every single molecule in the body that’s tweaked or turned on by exercise.

This kind of study–its size, its rigor, its aims–is a first, and experts are hoping it will give doctors the evidence they need to start treating exercise like the miracle drug they’ve long thought it to be. “If you think of exercise as a true form of medicine, which it is, it’s not good enough to just look at a patient and say, ‘You need to do more exercise,'” says Bamman, director of the Center for Exercise Medicine at the University of Alabama at Birmingham. “That’s no better than handing someone a bottle of pills and saying, ‘Here, take a few,'” with no other explanation.

Bamman is betting that with this new data, exercise will one day be prescribed to patients. Instead of leaving the doctor’s office with nothing but a slip of paper with a drug name scrawled on it, patients may also get a detailed exercise plan tailored to make their medication work better. “We think that precision will go a long way in changing behavior,” Bamman says. “We’re at a really important time in the field.”

Think of all the different ways you can sweat and you might be surprised that each falls into one of just two categories. You’re doing aerobic exercise when your breathing speeds up, your blood flows faster and your heart pumps more of it, shooting oxygen out to the tissues in the rest of the body. It’s the most popular kind; about half of Americans meet the recommendations for aerobic physical activity. But only 20% also do the other type, strength training. The phrase may conjure grunting weight lifters and gym dumbbells slick with sweat, but to build muscle and strengthen bones, you really only need to use your body weight as resistance, says Anthony Hackney, an exercise physiologist at the University of North Carolina at Chapel Hill. That’s why things like yoga, tai chi and Pilates–not just pumping iron–are excellent forms of strength training. “People always get the image of the big, muscular guy,” Hackney says. “We try to think of muscle strength and power as a 65-year-old lady picking up a gallon of milk, pouring a glass and feeling comfortable.”

In addition to the heart, muscles, lungs and bones, scientists are finding that another major beneficiary of exercise might be the brain. Recent research links exercise to less depression, better memory and quicker learning. Studies also suggest that exercise is, as of now, the best way to prevent or delay the onset of Alzheimer’s, which is second only to cancer as the disease Americans fear most, according to surveys.

Scientists don’t know exactly why exercise changes the structure and function of the brain for the better, but it’s an area of active research. So far, they’ve found that exercise improves blood flow to the brain, feeding the growth of new blood vessels and even new brain cells, courtesy of the protein BDNF, short for brain-derived neurotrophic factor. BDNF triggers the growth of new neurons and helps repair and protect brain cells from degeneration. “I always tell people that exercise is regenerative medicine–restoring and repairing and basically fixing things that are broken,” Bamman says.

Repairs like this throughout the body may be the reason exercise has been shown to extend life span by as much as five years. A small new study suggests that moderate-intensity exercise may slow down the aging of cells. As humans get older and their cells divide over and over again, their telomeres–the protective caps on the end of chromosomes–get shorter. To see how exercise affects telomeres, researchers took a muscle biopsy and blood samples from 10 healthy people before and after a 45-minute ride on a stationary bicycle. They found that exercise increased levels of a molecule that protects telomeres, ultimately slowing how quickly they shorten over time. Exercise, then, appears to slow aging at the cellular level.

For all its merits, however, exercise is not an effective way to lose weight, research has shown. In a cruel twist, many people actually gain weight after they start exercising, whether from new muscle mass or a fired-up appetite. “Some people say exercise doesn’t do anything,” says researcher John Jakicic of the University of Pittsburgh. “Well, exercise does a lot. It just may not show up on the scale.”

One of the best pieces of news is that so much of what we already do counts as physical activity. “Mowing the grass, raking leaves, washing the car–all that’s exercise,” says Berryman, the exercise historian. “Physical activity includes all movement, not just throwing a ball through a basket.”

What’s more, emerging research suggests that it doesn’t take much movement to get the benefits. “We’ve been interested in the question of, How low can you go?” says Martin Gibala, an exercise physiologist at McMaster University. After all, if it were possible to reap all the health benefits of exercise in a tiny fraction of the time, who wouldn’t be compelled to give it a try?

Gibala wanted to test how efficient and effective a 10-minute workout could be, compared with the standard 50-minutes-at-a-time approach. The micro-workout he devised consists of three exhausting 20-second bouts of all-out, hard-as-you-can exercise, followed by brief recoveries. In a three-month study, he pitted the short workout against the standard one to see which was better.

To his amazement, the workouts resulted in identical improvements in heart function and blood-sugar control, even though one workout was five times longer than the other. “If you’re willing and able to push hard, you can get away with surprisingly little exercise,” Gibala says.

Not everyone can–or wants to–do this kind of excruciating workout, often referred to as high-intensity interval training, or HIIT. Many of us would gladly bounce around in Zumba class for an hour to avoid enduring even a minute of HIIT torture. But considering that a lack of time is the No. 1 reason people say they don’t exercise, a workout far shorter than what’s generally recommended could be a strong motivator. Gibala, for his part, is wondering if the workout can get even shorter. He’s even played around with the idea of a one-minute workout.

Not every type of exercise will work for every person, of course, but a growing body of research indicates that very vigorous exercise–like the interval workouts Gibala is studying–is, in fact, appropriate for people with different chronic conditions, from Type 2 diabetes to heart failure. That’s new thinking, because for decades, people with certain diseases and even pregnant women were advised not to exercise. Now scientists know that far more people can and should exercise. A recent analysis of more than 300 clinical trials discovered that for people recovering from a stroke, for instance, exercise was even more effective at helping them rehabilitate.

Dr. Robert Sallis, a family physician who runs a sports-medicine fellowship at Kaiser Permanente Fontana Medical Center in California, has prescribed exercise to his patients since the early 1990s in hopes of doling out less medication. “It really worked amazingly, particularly in my very sickest patients,” he says. “If I could get them to do it on a regular basis–even just walking, anything that got their heart rate up a bit–I would see dramatic improvements in their chronic disease, not to mention all of these other things like depression, anxiety, mood and energy levels.”

Older people, too, can benefit from strenuous exercise. Until now, all the recommendations for increasing bone density have included low-repetition, high-weight types of training, says Jinger Gottschall, associate professor of kinesiology at Penn State University. “But this just isn’t feasible for a lot of people. You can’t picture your grandma going in and doing that.” Luckily for Grandma, Gottschall’s team found that lifting lighter weights for more reps improves bone density in key parts of the body, making it a good alternative to heavy lifting.

It’s becoming evident that nearly everyone–young, old, pregnant, ill–benefits from exercise. And as scientists learn more about why that is, they’re hoping that those early 20th century missteps–the move away from our being bodies in motion–will be reversed. They’re also hoping that the messaging around exercise gets simpler. “People think now, because of the health-club and fitness movement, that in order to exercise you need to join a fancy club and wear fancy clothes,” says Berryman. In fact, some of the best exercise, research is showing, doesn’t require a gym membership at all.

Back at McMaster University, Tarnopolsky and his team are almost finished doing autopsies on mice from their new study, and even though the scalpel-wielding scientists are blind to which groups the mice were in, they can tell with certainty which animals were allowed to exercise and which were sedentary. “You open up the sedentary mice and there’s fat all over the place,” he says. About half of those mice have tumors. “They just look god-awful.”

As for the mice who hit the wheel every day? “We haven’t found a single tumor,” he says. “I think if people saw, they’d be pretty motivated to exercise.”

This appears in the September 12, 2016 issue of TIME.

Write to Mandy Oaklander at mandy.oaklander@time.com.