Humans are meant to move
IN 1966, a team of physiologists in Dallas, Texas, decided to compare the effects of sedentariness versus exercise on health by paying five healthy 20-year-olds to spend three weeks in bed, followed by an intensive eight-week exercise program. The bed rest was ruinous. When they were finally allowed to arise from their beds, the volunteers’ bodies resembled 40-year-olds by many metrics: they were fatter, had higher blood pressure, higher cholesterol levels, less muscle mass, and lower fitness. The eight ensuing weeks of exercise, however, not only reversed the deterioration but in some cases led to net improvements. To the lead researcher, Bengt Saltin, the take-home message was simple: “Humans were meant to move.” Time marches on, however, and to evaluate how aging affects the effects of inactivity, researchers had the bright idea of restudying the same five volunteers 30 years later.
Three decades of typical American lifestyles had not been kind to the original volunteers: they had each gained about 50 pounds, had higher blood pressure and weaker hearts, and were less fit and healthy in numerous ways. But they agreed to be studied once more as they tried to undo the consequences of 30 sedentary years with a six-month program of walking, cycling, and jogging. Fortunately, this second late-in-life exercise intervention helped the volunteers lose about 10 pounds, and, most astoundingly, largely reversed their decline in cardiovascular fitness. After six months of moderate exercise, the average volunteer’s blood pressure, resting heart rate, and cardiac output returned to his 20-year-old level. Many other studies confirm the anti-aging benefits of exercise. But few of them explain why.
The most common explanation for why exercise slows and sometimes turns back the gradual slide toward poor health is that physical activity prevents or ameliorates bad things that accelerate senescence. Top of the list is fat. Exercise staves off and sometimes reverses the accumulation of excess fat, especially belly fat, a chief cause of inflammation and other problems. Exercise also lowers bloodstream levels of sugar, fat, and unhealthy cholesterol that slowly contribute to hardening of the arteries, damage proteins, and otherwise gum up the works. And as trials like the Dallas Bed Rest Study show, exercise also improves cardiovascular function, lowers levels of stress hormones, revs up metabolisms, strengthens bones, and more. Yet these and other salubrious effects of exercise explain only how but not why physical activity combats senescence. To understand why physical activity activates dozens of processes that maintain function and repair some of the damage that accumulates with age, we need to explore what I term the Costly Repair Hypothesis.
To introduce this idea, let’s follow (with her permission) what happened to my wife when she included a hard gym workout as part of a typical Saturday. For the first few hours that day, my wife was either sedentary or did light physical activities. Then at 10:00 A.M. she went to the gym and did 45 minutes of vigorous cardio before a demanding 45-minute workout with weights. Afterward, she was not only tired but also slightly sore.
Importantly, my wife’s exercise session was not only calorically costly but also physiologically stressful. As she struggled to complete her cardio and weight workouts, her body’s “fight and flight” system released cortisol, epinephrine, and other stress-related hormones to speed up her heart and mobilize her energy reserves. As her muscles rapidly consumed calories, they pumped out waste compounds that compromised her cells’ functions, and her mitochondria leaked an abundance of harmful reactive oxygen species that damaged DNA and other molecules throughout the body. To add injury to insult, her hard-working muscles also developed microtears as she struggled with heavy weights. All in all, beyond causing discomfort, my wife’s strenuous workout generated some short-term damage.
If exercise is so destructive, why is it healthy? One explanation is that once she stopped exercising, my wife’s body reacted by repairing whatever harm she caused and, crucially, also repairing some of the damage that she had accumulated beforehand when she wasn’t exercising. As a result, she restored many tissues to their previous state. To deal with the tissue damage caused by her workout she mounted an initial inflammatory response followed by a later anti-inflammatory response. She also produced copious, powerful antioxidants to mop up the reactive oxygen species unleashed by her mitochondria. And she turned on a host of other processes to rid her cells of waste products, repair DNA mutations, damaged proteins, and epigenetic modifications, as well as mend cracks in her bones, replace and add mitochondria, and more.
While exercise restores most structures (what biologists term homeostasis), in some cases it may create stability by making things even better than before (allostasis). For example, demanding physical activities can increase the strength of bones and muscles, increase cells’ abilities to uptake glucose from the blood, and both augment and replace mitochondria in muscles. In addition, repair mechanisms sometimes overshoot the damage induced by exercise, leading to a net benefit. It’s like scrubbing the kitchen floor so well after a spill that the whole floor ends up being cleaner. All in all, the modest physiological stresses caused by exercise trigger a reparative response yielding a general benefit, a phenomenon sometimes known as hormesis.
If you are entrepreneurial, hate exercise, or both, these beneficial responses may have ignited a lightbulb. Instead of going through the bother and discomfort of exercising, why not find some easier, preferably consumable way to turn on the same maintenance and repair mechanisms? Why not just take a pill? Without breaking a sweat, I can buy vitamins C and E and beta-carotene to boost my antioxidant levels, and purchase capsules loaded with turmeric, omega-3 fatty acids, and polyphenols that fight inflammation.
The problem is that dozens of studies have found that taking antioxidant pills is no substitute for physical activity to fight senescence. Three or four studies reported a modest benefit, but the rest found that antioxidants provided no benefit or even increased the risk of dying. To add insult to injury, additional studies suggest antioxidants may sometimes do more harm than good when combined with exercise. This head-turning conclusion followed from a groundbreaking 2009 experiment by Michael Ristow, a researcher in Zurich who studies aging and metabolism. His team asked 40 healthy young males with varied fitness levels to undergo four weeks of supervised exercise. Half the participants were given large doses of vitamins C and E, the other half received a placebo. Muscle biopsies taken before and after their exercise bouts showed that, as expected, physical activity induced plenty of oxidative stress, but those who took antioxidants incurred more oxidative damage because their bodies produced much lower levels of their own antioxidants. The antioxidant pills apparently suppressed the body’s normal anti-stress response, probably because oxidative damage from exercise itself is needed to trigger the body’s health-promoting antioxidative defense mechanisms.
Why is regular physical activity the best way to delay senescence and extend life?
Recall that according to the Costly Repair Hypothesis, organisms with restricted energy supplies (just about everyone until recently) must allocate limited calories toward either reproducing, moving, or taking care of their bodies, but natural selection ultimately cares only about reproduction. Consequently, the cold calculus of selection prefers us to spend as little energy as possible on costly maintenance and repair tasks. So while physical activities trigger cycles of damage and restoration, selection favors individuals who allocate enough but not too much energy to producing antioxidants, enlarging and repairing muscles, mending bones, and so on. The challenge is to maintain and repair any damage from physical activity just enough and in the right place and the right time.
Evolution’s stingy solution to this problem is to match capacity in response to demand. In this case, the demand is the stress caused by physical activity, especially reactive oxygen species and other damaging processes that stiffen arteries, mutate genes, and gunk up cells. The capacity is the ability to maintain, often through repair, a stable internal environment so we can adequately and effectively perform those functions needed for survival and reproduction. And, crucially, the maintenance and repair mechanisms activated by physical activity don’t cease to function as we age. Although some become less responsive, they keep on ticking, allowing physically active post-reproductive individuals to slow or delay senescence.
Unfortunately, this marvelous system has one big flaw. Apparently, we never evolved to activate these maintenance and repair responses as effectively in the absence of regular physical activity. As we have seen, almost no one in the Stone Age, least of all grandparents, managed to avoid hours of walking, running, digging, climbing and other manual labors. Hunter-gatherers of all ages would have stimulated their body’s natural reparative mechanisms nearly every day in response to the demands posed by their way of life. So just as our species never evolved to diet or cope with jetlag, we never evolved to counter many aging processes to the same degree without physical activity.
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