CHAPTER SEVEN
Training Your Telomeres: How Much Exercise Is Enough?
Exercise reduces oxidative stress and inflammation, so it’s not surprising certain exercise programs have also been shown to increase telomerase. However, weekend warriors should beware: overdoing a workout can actually promote oxidative stress, and overdoing it on a chronic basis (overtraining) may cause serious damage to you and your telomeres.
In May 2013, Maggie ran her first ultramarathon. She had been a strong contender in shorter races, and she liked the idea of pushing herself to run very long distances, like this hundred-mile race through the desert. She didn’t even let herself hope that she might take a top spot; she just wanted to finish. Halfway through the ultramarathon, one of Maggie’s friends met up with her and said, “Did you know you’re in thirteenth place? You could finish in the top ten!”
Maggie decided to dig deeper. Over the next several hours, she overtook the twelfth-place runner, and then the eleventh, and then the tenth. She crossed the finish line in tenth place, guaranteeing that she would be invited back the next year to run in a place of honor.
That summer, Maggie ran three more ultramarathons: another hundred-miler in June, and two more in July and August. She felt great. In September, she decided that instead of taking a long recovery period from her grueling workout schedule, she’d train for another ultra in December. Then, suddenly, a few weeks into training, Maggie virtually stopped sleeping. She spent entire nights wide awake; she would sit up in bed and watch as her phone lit up in the morning, its alarm ringing. “I’ve never done drugs, but I imagine this is what being on speed is like,” Maggie says. “I couldn’t sleep, and I wasn’t tired. I had a ton of energy. It was very weird.”
Maggie continued to train. Then the illnesses set in: colds, the flu, other viruses. She tried cutting back on her workouts, but she didn’t notice an improvement in her symptoms, so she resumed her schedule. Then, in early winter, her body broke down. She couldn’t complete her workouts. She could barely get to work. She could barely get out of bed.
Maggie had nearly all the signs of overtraining syndrome, an unofficial diagnosis that is characterized by sleep changes, fatigue, moodiness, vulnerability to illness, and physical pain.
When Maggie reminisces about her “grand slam summer” of ultramarathons, the people around her have mixed reactions. Some are judgmental—they declare, almost gleefully, that such intense exercise is bound to be bad for the human body. Others feel guilty. Despite Maggie’s troubles, they feel that something is wrong with them if they’re not working out at this elite level. Others use Maggie’s experience as an excuse not to work out at all.
Exercise can be a confusing topic; it can also be an emotional one. But telomeres offer some clarity. Telomeres do not need extreme fitness regimens to thrive, and that is good news for all of us who feel discouraged when we meet people like Maggie, who spent her grand slam summer taking her body to the breaking point and then past it. Another piece of good news is that telomeres appear to respond powerfully to many different levels and types of exercise. In this chapter, we’ll show what the range of healthy exercise looks like and how you can gauge whether you are doing too little—or, as in Maggie’s case, too much.
TWO PILLS
Let’s pretend you’re at a drugstore of the future. You consult with the pharmacist, who gives you a choice between two pills. You point to the first one and ask what it does.
The pharmacist ticks the benefits off on her fingers. “Lowers your blood pressure, stabilizes your insulin levels, improves your mood, increases your calorie burn, fights osteoporosis, and cuts your risk of stroke and heart disease. Unfortunately, its side effects include insomnia, skin rash, heart problems, nausea, gas, diarrhea, weight gain, and lots of others.”
“Hmmm,” you say. “How about the second pill? What does it do?”
“Oh, it’s got the same benefits,” the pharmacist says brightly.
“And the side effects?” you ask.
She beams. “There aren’t any.”
The first pill is imaginary, a fantasy synthesis of beta-blockers to control high blood pressure, statins to reduce cholesterol, diabetes drugs to regulate insulin, antidepressants, and osteoporosis medications.
The second pill is real, sort of. It’s called exercise. People who exercise live longer and have a lowered risk of high blood pressure, stroke, cardiovascular disease, depression, diabetes, and metabolic syndrome. And they avoid dementia for longer.
If exercise is like a drug that pumps wondrous effects through your entire physiology, how does it work? You already know the macro view of exercise. It increases blood flow to your heart and your brain, builds muscle, and strengthens your bones. But if you could take a powerful microscope to exercise’s effects, and peer into the heart of human cells when they are regularly exercised, what would you see?
Calmer, Slimmer, and Better at Fighting Free Radicals: The Cellular Benefits of Exercise
People who exercise spend less time in the toxic state known as oxidative stress. This noxious condition begins with a free radical, a molecule that is missing an electron. A free radical is rickety, unstable, incomplete. It craves the missing electron, so it swipes one from another molecule—which is now unstable itself and needs to steal a replacement electron of its own. Like a dark mood that is passed from one person to another, each person feeling a little better the bad feelings are dumped onto someone else, oxidative stress is a state that can shear through a cell’s molecular population. It’s associated with aging and onset of the diseasespan: cardiovascular disease, cancer, lung problems, arthritis, diabetes, macular degeneration, and neurodegenerative disorders.
Fortunately, our cells also contain antioxidants, which offer natural protection against oxidative stress. Antioxidants are molecules that can donate an electron to a free radical but still remain stable. When an antioxidant gives an electron to a free radical, the chain reaction ends. An antioxidant is like a wise friend who says, “Okay, tell me all your bad feelings; I’ll listen and you’ll feel better, but I’m not going to let you make me feel bad, too. And I’m definitely not going to pass your black mood on to someone else.”
In an ideal situation, your cells have enough antioxidants to keep up with the need to neutralize free radicals in your body. Free radicals will never be completely eradicated from our bodies. They are continuously being made by the very processes of life—they occur normally through metabolism. In fact, very small numbers of free radicals are important for the normal communication processes in our cells. But radicals can also be created in excess when you’re exposed to environmental stresses like radiation and smoking, or to severe depression. The danger seems to occur when free radicals build up. And when you have more free radicals than antioxidants, you enter an imbalanced state of oxidative stress.
That’s one reason exercise is so valuable. In the short term, exercise actually causes an increase in free radicals. One reason is that you’re taking in more oxygen. Most of those oxygen molecules are used to create energy from special chemical reactions in the mitochondria in your cells, but an unavoidable by-product of these vital processes is that some of them also form free radicals. But that short-term response creates a healthy counterresponse: The body steps up by producing more antioxidants. Just as short-term psychological stress can toughen you up and increase your ability to handle difficulty, the physical stress of moderate-intensity regular exercise ultimately improves the antioxidant–free radical balance so that your cells can stay healthier.
Your cells soak up the benefits of exercise in other ways, too. When you exercise regularly, the cells in your adrenal cortex (located inside your adrenal glands) release less cortisol, the notorious stress hormone. With less cortisol, you feel calmer. With regular exercise, cells throughout your body become more sensitive to insulin, which means your blood sugar is more stable. If you want to avoid the common midlife trifecta of stress, belly weight gain, and high blood sugar, you need to exercise.
Immunosenescence: Exercise Can Keep You in the Healthspan Longer
Immunosenescence is an important process underlying increased sickness and malignancy as we age. As a result of immunosenescence, you experience higher circulatory levels of proinflammatory cytokines, molecules that can spread inflammation through the body like a fire whipped along by gusts of wind. This hastens more of your T-cells toward senescence so they can’t do their work of fighting off sickness. Some senescent immune cells, as you know from earlier in the book, can even go rogue. These aging immune cells can leave you more vulnerable to the kind of nasty bugs that can put you into a hospital bed. If you have a lot of immunosenescent cells and you get a vaccine for pneumonia or this year’s strains of flu, there’s a good chance the vaccine won’t “take” and that you’ll end up feverish and coughing anyway.1 Your aging cells make it harder for you to enjoy the benefits of preventive medicine.
However. Compared to couch potatoes, people who exercise regularly have lower inflammatory cytokine levels, respond more successfully to vaccinations, and enjoy a more robust immune system. Immunosenescence is a natural process that happens with age… but people who exercise may be able to delay it until the end of life. As the exercise and immunology researcher Richard Simpson has said, these and other signs “indicate that habitual exercise is capable of regulating the immune system and delaying the onset of immunosenescence.”2 Consider exercise an excellent bet for keeping your immune system biologically young.
WHAT KIND OF EXERCISE IS BEST FOR TELOMERES?
Exercise helps protect your cells by warding off inflammation and immunosenescence. Now there is an additional explanation of exercise’s cellular benefit: exercise helps you maintain your telomeres. This was true even in a study of 1,200 twin pairs, which allowed exercise’s effects to be teased apart from effects of genetics: the active twin had longer telomeres than the less active twin.3 After adjusting for age and other factors that affect telomeres, by statistically removing their effect, the relationship between telomeres and activity was laid bare. And it’s not just that exercise is helpful; we also know that sedentariness itself is terrible for metabolic health. Now several studies have found that sedentary people have shorter telomeres than people who are even a little more active.4
But are all types of exercise equal when it comes to cell aging? Researchers Christian Werner and Ulrich Laufs of Saarland University Medical Center in Homburg, Germany, tested three types of exercise in a small but exciting study. Their results hint that exercise really may increase telomerase’s replenishing action—and they help us understand which kinds of exercise are best for keeping our cells healthy. Two kinds of exercise stood out. Moderate aerobic endurance exercise, performed three times a week for forty-five minutes at a time, for six months, increased telomerase activity twofold. So did high-intensity interval training (HIIT), in which short bursts of heart-pounding activity are alternated with periods of recovery. Resistance exercise had no significant effect on telomerase activity (although it had other benefits; the researchers concluded that “resistance exercise should be complementary to endurance training rather than a substitute”). And all three forms of exercise led to improvements in telomere-associated proteins (such as telomere-protecting protein TRF2) and reduced an important marker of cellular aging known as p16.5 They also found that regardless of exercise type, those who increased their aerobic fitness the most had greater increases in telomerase activity. This tells us it’s the underlying cardiovascular fitness that matters most.
So try to do moderate cardiovascular exercise or HIT. Either is great. Our Renewal Lab at the end of this chapter will show you these evidence-based workouts for strengthening your telomeres. You may not want to restrict yourself to just one type of workout, though. We benefit from variety. In a study of thousands of Americans, the more categories of exercise—from walking to biking to strength training—that people engaged in, the longer their telomeres.6 And this is a reason to perform strength training. Even though strength training doesn’t appear to be significantly related to longer telomeres, it helps maintain or improve bone density, muscle mass, balance, and coordination—all of which are vital for aging well.
How, exactly, does exercise strengthen telomeres?
Maybe the wonderful cellular effects of exercise, including less inflammation and oxidative stress, are good for telomeres. Or maybe exercise is good for telomeres because it prevents stress from causing some of its usual damage. The stress response can leave cellular damage and debris in its wake—but exercise switches on autophagy, the housekeeping activity in the cell that eats up those damaged molecules and recycles them.
It’s also possible that exercise improves telomeres directly. For example, getting on the treadmill induces an acute stress response, which increases the expression of TERT, a telomerase gene.7 Athletes have higher expression of TERT than sedentary people.8 Exercise releases a newly identified hormone, irisin, that boosts metabolism and in one study was associated with longer telomeres.9
But no matter how the exercise-telomere connection works, what’s most significant is that exercise is essential for your telomeres. To keep your telomeres healthy, you need to work them out. For the workouts that have been shown to improve telomere maintenance, see the Renewal Lab.
GAUGE YOUR TELOMERE FITNESS
It’s not simply working out that is crucial for telomere health. As we hinted earlier, fitness, the ability to perform physical tasks, is important, too. It is very possible for someone to perform light regular exercise, but not be fit. And some lucky people can be fit without exercising, especially when they’re young. (Think of twentysomethings who can successfully complete a long, arduous hike even if they haven’t worked out since high school.) For telomere health, you need to get regular exercise and you need to be fit.
But how fit do you need to be? Do you need to be capable of running ultramarathons, like Maggie? Swim five miles in the open water? Do you have to be like one of our Midwestern friends, who spends Saturday mornings in October at races featuring “zombies” who chase her through fields of corn? Our cultural standards for fitness are getting higher and higher, and it can be hard to know whether you are fit enough to stay healthy.
Fitness is, in fact, crucial for telomere health.12 But you may be relieved to know that significant telomere benefits are gained by having a very moderate, achievable level of fitness. Our colleague Mary Whooley, of UCSF, put a group of adults, all of whom have heart disease, on a treadmill. They began by walking, with the incline and speed gradually increased until they could do no more. The results were clear: The less exercise capacity they had, the shorter their telomeres.13 The people with the lowest cardiovascular fitness couldn’t even sustain a brisk walk, whereas those most fit sustained the equivalent pace to taking a hike. Those with low fitness had fewer base pairs by an amount that translates to about four years of extra cell aging, compared to the fit group.
Are you able to mow your lawn? Shovel snow? Carry your own clubs while playing golf? If not, you are in this category of low fitness. There are easy ways to slowly and safely build your capacity. Check with your doctor and then consider our walking plan, in the Renewal Lab. On the other hand, if you can walk vigorously or maintain a light jog for forty-five minutes, three times a week, you are fit enough to support your telomere health. Remember that fitness and exercise are related, but separate. Even if you are naturally fit, you still need an exercise program to keep your telomeres healthy.
TOO MUCH EXERCISE?
Moderate exercise and fitness are clearly wonderful for telomeres, but what about Maggie, the ultramarathon runner? Are her telomeres longer because she took exercise to the extreme? Are they shorter? Few of us run ultramarathons, but as more people participate in endurance sports, questions like these become more urgent.
Most extreme exercisers can breathe a sigh of relief. One remarkable study of ultrarunners found that their cells were the equivalent of sixteen years younger than those of their sedentary counterparts.14 Does this mean that we should all sign up for the next hundred-mile race? Not at all. Those ultrarunners were compared to sedentary people. When endurance athletes are compared to more ordinary runners, who might run around ten miles a week, you find that both groups have nice, healthy telomeres compared to the more sedentary group—and that there appears to be no additional benefit for the ultra-long-distance endurance group in terms of telomeres.15
Endurance athletes sometimes worry about whether it’s safe to continue their extreme training year after year, as opposed to training for a single endurance event and then returning to a more typical exercise routine. One study looked at older men who had been elite athletes when they were younger. Their telomeres were similar in length to other men their age, so their many years of extremely vigorous training didn’t appear to have had a cumulative wearing effect.16 Another German study examined a group of senior “master athletes” who had been competing in endurance races since their youth. Most of them still compete, just at a slower rate (such as taking eight hours instead of two to complete a marathon). The long-term athletes both looked younger and had less telomere shortening compared to matched controls.17 Another study examined years of exercise and found longer telomeres in people who had actively exercised for the past ten years or more.18 It appears important to start exercising when you are young—but don’t be discouraged. It’s never too late to start, and benefits always await you.
Maggie, however, may be in some trouble. One study of extreme exercisers found that they had shorter muscle telomere length—but only if the exercisers suffered from a fatigue-overtraining syndrome.19 When athletes develop a fatigue syndrome, as Maggie did, it is a sure sign they have overtrained and damaged their muscles to the extent that they can’t be easily repaired. Progenitor cells (also known as satellite cells) repair muscle tissue that has been damaged—but it is thought that overtraining damages those crucial cells, leaving them less able to do their repair work. It appears to be overtraining, not extreme exercise, that is damaging to telomeres, at least in the muscle cells.
Overtraining is defined by too much training time relative to rest and recovery. It can happen to anyone, from beginning runners to professional athletes, and it happens when you don’t support your body with enough rest, nutrition, and sleep. Psychological stress can contribute, too. Some warning signs of overtraining include fatigue, moodiness, irritability, trouble sleeping, and susceptibility to injuries and illness. The cure is rest—which sounds easy but is hard for athletes who are accustomed to pushing themselves.
Any discussion of overtraining is complicated, because there is no set point that constitutes “too much exercise.” That point is different for everyone, and it depends on individual physiology and level of training. If telomeres tell us anything, they remind us of how context-dependent health can be. What is good for one person may be harmful to another. If you are an extreme athlete, make sure you’re working closely with a trainer or physician so that any signs of overtraining can be spotted early.
In general, it’s a good idea to begin any exercise program slowly, gradually working up to better fitness. Weekend warriors who sit in the office for five days and then overdo it on the weekend, pushing themselves to break down a lot of muscle at once, will feel fatigued and sometimes even nauseated. They are not doing their bodies any favors. Remember that exercise initially creates additional oxidative stress in the body, and then there is a healthy counterresponse that reduces that stress. But if you overdo it, that counterresponse can be overwhelmed. You’ll end up with more oxidative stress, not less.
STRESSED OR DEPRESSED? EXERCISE IS RESILIENCE TRAINING FOR YOUR CELLS
“I don’t have time to exercise. I’m already overcommitted and overscheduled.”
“I’ll exercise when I feel better. I am so stressed right now that I can’t push myself to do one more hard thing.”
Sound familiar? Yet it turns out that the most important time to exercise is exactly when you might not want to—when you are feeling overwhelmed. Exercise can improve your mood for up to three hours after working out20 and can reduce stress reactivity.21 Stress can shorten telomeres, but exercise shields telomeres from some of stress’s damage. Our colleague Eli Puterman, a psychologist and exercise researcher at the University of British Columbia, has studied high-stress women, including many stressed-out caregivers. The more the women exercised, the less their stress ate away at their telomeres (see figure 17). The exercise actually buffered their telomeres from the insidious and telomere-shortening effects of stress. Even if your schedule is packed, even if you feel too exhausted to do a hard workout, find a way to slip in some exercise. For example, the two of us maintain busy schedules, but while working on this book we took walks together, thinking through the chapters aloud as we went up and down the hills of San Francisco.
Figure 17: Physical Activity May Buffer Stress-Related Telomere Shortening. Women high on perceived stress had shorter telomeres, but only if they were relatively sedentary. If they exercised, they did not show the stress-telomere relationship.22 The raw values (unadjusted) for telomere length in base pairs are shown here on the vertical axis.
You can probably exercise more often than you realize. But on the days when you just can’t make it happen, take heart. In psychology, resilience is a kind of Holy Grail. Resilience is what keeps you bouncing back after being knocked down and lets stress slide off your shoulders without damaging your mind and body. Eli Puterman’s stress research shows that telomeres can be resilient, too. The more you can practice good health habits—effective emotion regulation, strong social connections, good sleep, and good exercise—the less that stress hurts your telomeres. This is especially true if you have depression.23 Exercise is a potent way to make your telomeres resilient, but when you can’t exercise, step up other resiliency behaviors. Everything you do will help, and that’s an encouraging piece of news.
TELOMERE TIPS
People who exercise have longer telomeres than those who don’t. This is true even for twins. It’s the increased aerobic fitness that is most tied to good cell health.
Exercise charges up the cell clean-up crew, so that cells have less junk buildup, more efficient mitochondria, and fewer free radicals.
Endurance athletes, who have the best fitness and metabolic health, have long telomeres. But those telomeres are not much longer than those with moderate exercise. We don’t need to aspire to extremes.
Athletes who overexercise and burn out develop many physical issues, including risk of shorter telomeres in their muscle cells.
If you have a high-stress life, exercise is not just good for you. It is essential. It protects you from stress-shortened telomeres.