9

Aging

The Wise Way

MY MOTHER WAS known as the fast walker. At five foot six, she ruled the sidewalks in our western Pennsylvania town, and people would always ask my brother and sister and me where she was running off to. She would stride to church for the early Mass every morning except Sunday, when my father drove all of us in our good clothes. It was a mile and a half each way, which was a pretty good workout at her pace, but she didn’t walk to stay in shape. She walked because she liked to walk (and to compare prices at grocery stores a mile apart).

Judging from what scientists have learned about the nourishing effects of exercise on the brain, I’m certain that my mother’s level of physical activity is what kept her so sharp for so long. Well into her eighties, Vern Ratey lived a full, vibrant life. Part of that was just her personality — she always had to be doing something. I remember that we bought a couch once, after she stewed for weeks over the color and size, measuring and remeasuring. The day it was delivered, I arrived home from school to find her busy sawing off the upholstered arms so that our new piece of furniture would fit as she’d wanted it to.

It was with the same unvarnished zeal that she attended to everything, whether planting tomatoes in a craggy patch alongside the house or shoveling snow. She was a professional volunteer — my father wouldn’t let her work — and our basement was full of donated clothing for church rummage sales, which meant we got first pick. As a second-generation working-class American from Czechoslovakia, she was certainly a product of the Depression: thrifty and stern, tough but loving.

My father, Stephen, was four years older, and he died when my mother was fifty-nine. Although it took her several years to recover, she was a resilient woman with lots of friends, and eventually she met another man and remarried in her midsixties. The two of them spent winters in Vero Beach, Florida, where he taught her how to play golf, and she learned how to swim. In the summer she’d wake up and put on her bathing suit beneath her clothes, so she could stop by the pool; her only stroke was the dog paddle, and she’d motor around for an hour at a time in the deep end. And she kept walking: to church, to the grocery store, to go dancing or bowling, and to play bridge at the senior center three times a week.

Aside from osteoporosis, her health was strong. And her wits were sharp. Whenever I called, we would have detailed conversations about her earning master points in bridge or how she should manage her money. Her second husband died when she was in her early seventies, but she kept moving.

When my mom was eighty-six, she tripped and broke her hip, which is just the sort of accident that sends about 1.8 million seniors to the emergency room every year. Although heart disease, cancer, stroke, and diabetes are the leading causes of death for Americans over age sixty-five, many of them live in fear of falling and breaking their brittle bones. Hip fractures are particularly devastating because they require months to rehabilitate, and losing mobility in such a pivotal, weight-bearing joint can dramatically reduce a person’s activity level. About 20 percent of older adults who break a hip die within a year.

As for my mom, after about six months she got back on her feet with the help of a walker, and we were able to avoid putting her in a nursing home by having a live-in aide. But it slowed her down — she was shuffling instead of walking — and her osteoporosis was progressing more rapidly, curling her spine and forcing her into a stoop. When her body slowed down, her mind followed suit: she stopped playing bridge and started watching soap operas. A friend took her to church on Sundays, but otherwise she didn’t get out much. She was slipping mentally, but didn’t have dementia yet — she knew perfectly well who I was, but she had less and less to say during our conversations.

Then, the following year, she fell and broke her other hip. It was crushing for me to see her immobilized, and that’s when she really stopped being herself. She lost her grip on the boundaries between what was real and what was not. The soap opera characters became part of her life, and she talked to them as if they were right there in the room. She died of natural causes at eighty-eight.

KEEPING IT ALL TOGETHER

I’ve talked a lot about the biological connections between the body and the brain throughout this book, and nowhere are they more important than in the discussion of aging. After all, a sound mind won’t do you much good if your body fails.

In 1900, the average American could expect to live to age forty-seven. Today, life expectancy is over seventy-six, and when older folks die, the reason is more likely to be chronic disease than acute illness. But those who outlive these odds face other daunting statistics: The average seventy-five-year-old suffers from three chronic medical conditions and takes five prescription medicines, according to the Centers for Disease Control (CDC). Among those over sixty-five, most suffer from hypertension; more than two-thirds are overweight; and nearly 20 percent have diabetes (which triples the chance of developing heart disease). The leading killers are heart disease, cancer, and stroke; together they account for 61 percent of all deaths in this age group.

We already know that smoking, inactivity, and eating poorly are root causes of these bodily diseases. Likewise, the latest research is clear about how lifestyle influences the mental hazards that come with aging. The same things that kill the body kill the brain, which neuroscientist Mark Mattson, of the National Institute on Aging, sees as a positive. “I think the good news — if we take it seriously — is that many of the same factors that can reduce our risk for cardiovascular disease and diabetes also reduce the risk for age-related neurodegenerative disorders,” he says. The measures we would take to guard against diabetes, for example, also balance insulin levels in the brain and shore up neurons against metabolic stress. Running to lower our blood pressure and strengthen our heart also keeps the capillaries in the brain from collapsing or corroding and causing a stroke. Lifting weights to prevent osteoporosis from devouring our bones releases growth factors that make dendrites bloom. Conversely, taking omega-3 fatty acids for mental acuity strengthens our bones.

The mental and physical diseases we face in old age are tied together through the cardiovascular system and metabolic system. A failure of these underlying connections explains why people who are obese are twice as likely to suffer from dementia, and why those with heart disease are at far greater risk of developing Alzheimer’s, the most common form of dementia. Statistically, having diabetes gives you a 65 percent higher risk of developing dementia, and high cholesterol increases the risk 43 percent. We’ve had the medical proof that exercise protects against these diseases for decades, yet, according to the CDC, about a third of the population over sixty-five reports that they engage in no leisure-time activity. My hope is that if you understand how exercise can also protect your mind, you’ll take it to heart.

Some of the most persuasive evidence about the effect of exercise on the aging brain comes from a landmark research project called the Nurses’ Health Study, which began surveying the health habits of more than 122,000 nurses every two years, in the mid-1970s. In 1995 researchers began cognitive testing for some of the nurses, which allowed Harvard epidemiologist Jennifer Weuve to analyze the relationship between exercise level and cognitive ability for 18,766 women between seventy and eighty-one years old. Weuve used the trove of data to tackle the question of whether being active on a regular basis throughout adult life translates into sharper mental function when we’re older. The results, published in the Journal of the American Medical Association, powerfully underscored her hunch: women with the highest levels of energy expenditure had a 20 percent lower chance of being cognitively impaired on tests of memory and general intelligence. The median level of activity for this group translated to walking twelve hours a week, or running just under four hours total, compared with less than one hour of walking for the least active group (of five). But Weuve says you don’t have to be a “super athlete” to get a benefit. “The really neat thing is that we started to see effects at modest levels of activity — we’re talking about walking an hour and a half a week,” she says. Even at this relatively low level, “you start to see a benefit that is significantly above and beyond the least active women.”

HOW WE AGE

Getting older is unavoidable, but falling apart is not. Why is it that some people live to be one hundred with relatively few health problems, while others suffer from chronic diseases that rob them of normal mental and physical function? To understand how aging can take such divergent paths, it’s useful to have a look at life and death at the cellular level.

As we age, the cells throughout the body gradually lose their ability to adapt to stress. Scientists have yet to figure out exactly why this happens, but it’s clear that older cells have a lower threshold for combating the molecular stresses of free radicals, excessive energy demands, and overexcitability. And the genes responsible for producing proteins to clean up the damaging waste stop doing their job, which can lead to a cellular death spiral that neuroscientists call apoptosis. As the damage builds up, the immune system is activated and sends in white blood cells and other factors to mop up dead cells, which creates inflammation; if the swelling becomes chronic, it creates even more damaging proteins, and these are directly linked to Alzheimer’s.

In the brain, when neurons get worn down from cellular stress, synapses erode, which eventually severs the connections. With the decrease in activity, the dendrites physically shrink back and wither. Losing a signal here or there isn’t such a big deal at first, because the brain is designed to compensate by rerouting information around dead patches in the network and recruiting other areas to help with trafficking. There’s a certain redundancy built into the system. Remember, we’re talking about one hundred billion neurons, each of which might have up to one hundred thousand inputs. It’s a very social network that thrives on making new connections and, as I’ve mentioned, is constantly rewiring itself and adapting — provided there’s enough stimulation to spur the growth of new connections. As we get older, more real estate is required to carry out any given function. Wisdom, I think, is a reflection of how adept the brain is at compensating for this loss of efficiency.

If the synaptic decay outpaces the new construction, that’s when you start to notice problems with mental or physical function, ranging from Alzheimer’s to Parkinson’s disease (depending on where the degeneration occurs). Fundamentally, cognitive decline and all neurodegenerative diseases stem from dysfunctional and dying neurons; it’s a communication breakdown. Research on aging revolves primarily around the effort to “restore the nerve cells’ ability to communicate and stay alive,” Mattson points out. “If you can do that, then you can prevent their degeneration and therefore prevent the disease.”

As the synaptic activity decreases and dendrites retract, the capillaries feeding the brain shrink back as well, restricting blood flow. It can work the other way around too: if capillaries shrink back because you don’t get your blood pumping often enough, the dendrites follow suit. Either way, it’s a killer — without the oxygen, fuel, fertilizer, and repair molecules carried by the bloodstream, cells die. Levels of nurturing neurotrophins — such as brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) — trail off as you age too, and production of the neurotransmitter dopamine slows down, undermining motor function as well as motivation. Meanwhile, the hippocampus is getting fewer and fewer new neurons to work with. Studies in rats indicate that neurogenesis slows down dramatically with age — not because fewer stem cells are born, but because fewer of the starting pool divide and go on to become fully functioning neurons (probably due to less VEGF). Most neuronal stem cells die anyway, but the number that are put to use drops from about 25 percent to 8 percent in rodent middle age (approximately fifty years old for us) and then dwindles to 4 percent in old age (meaning over sixty-five). That’s to say nothing of the vast swaths of brain that don’t benefit from neurogenesis. Starting at about age forty, we lose on average 5 percent of our overall brain volume per decade, up until about age seventy, when any number of conditions can accelerate the process.

People like my mother who stay involved and active as they age can slow down the degeneration. In one study of recent retirees, researchers found that those who exercised maintained nearly the same level of blood flow in the brain after four years, while the inactive group had a significant decrease. If your brain isn’t actively growing, then it’s dying. Exercise is one of the few ways to counter the process of aging because it slows down the natural decline of the stress threshold. “Paradoxically,” says Mattson, “it’s good that cells be periodically subjected to mild stress because it improves their ability to cope with more severe stress.”

In addition, exercise sparks connections and growth among your brain’s cell networks in the same ways I’ve described in earlier chapters: it increases blood volume, regulates fuel, and encourages neuronal activity and neurogenesis. Because the aging brain is more vulnerable to damage, anything you do to strengthen it has a more pronounced effect than it would on a young adult. That’s not to say starting early isn’t important — if you have a better, stronger, more connected brain going over the hill, it will surely be more resilient and resist neuronal breakdown that much longer. Exercise is preventive medicine as well as an antidote. Age happens. There’s nothing you can do about the why, but you can definitely do something about the how and the when.

COGNITIVE DECLINE

It shows up in the little things first. As the connections in the brain break down, you have a harder time calling to mind people and places you’ve known. Everybody experiences this at some point — having something on the tip of your tongue but not being able to produce it. The prefrontal cortex, which is the search engine for your memory, can’t call it up. The hippocampus provides other associations to try to jog your memory, but it’s frustrating that you have to work so hard at something that used to happen subconsciously. This happens to most of us as we age, but the extent to which so-called mild cognitive impairment affects people varies dramatically.

It’s not necessarily progressive, but if mild cognitive impairment continues unchecked it can become dementia. You start to lose track of the events that have shaped who you are, which is a terribly threatening feeling that eats away at your sense of self. A lot of people who find themselves in this position tend to retreat, unknowingly mirroring their dendrites. They don’t venture out and make new connections for fear that they won’t know how to react, and they withdraw from the world, either out of embarrassment or simply because they feel uncomfortable outside the familiarity of home. Either way, the result is that they get cut off from meaningful relationships, which are an important form of stimulation for the brain. Isolation and inactivity feed the cellular death spiral, and this shrivels the brain.

The erosion is most pronounced in the frontal lobe, which encompasses both the gray matter of the prefrontal cortex and the white matter of its axons, and the temporal lobe, which catalogs words and proper names and helps form long-term memories through its tight connection to the hippocampus. If the prefrontal cortex goes, it takes higher cognitive functions with it, and that’s when the basic aspects of everyday life become trying. Ironically, the abilities we take for granted — being able to tie our shoes, unlock a door, or drive to the grocery store — rely on our highest order brain functions, such as working memory, task switching, and blocking out irrelevant information. That’s why even a trained monkey has trouble properly buttoning a shirt, and it’s probably why one of my patients always forgets to zip up his fly. At seventy-eight, he makes the same mistake over and over because — despite his wife’s haranguing — his working memory can’t hold onto the fact that he just used the bathroom.

The temporal lobe — our mental dictionary — is one of the areas that atrophies in Alzheimer’s disease. A simple test for the disease is to show someone a list of words and ask what she can recall half an hour later.

As I mentioned in the first chapter, researchers at the University of Illinois have conducted a number of studies showing a strong correlation between fitness levels and better performance on tests that target these brain areas. In one study, older adults who reported having a strong history of aerobic exercise clearly had better preserved brains, according to MRI scans. But a correlation is merely interesting to lab scientists. They wanted to see if exercise caused structural changes in these areas.

A team led by neuroscientist Arthur Kramer divided fifty-nine sedentary people ranging in age from sixty to seventy-nine into two groups that would hit the gym three times a week for one hour over the course of six months. Members of the control group embarked on a stretching routine, and the others walked on treadmills, starting out at 40 percent of their maximum heart rate and ramping up to 60 to 70 percent. The only variable was fitness, and indeed, after six months, the walking group averaged a 16 percent improvement in their maximal rate of oxygen consumption (VO2 max), which is a measure of the lungs’ capacity to process oxygen.

But the groundbreaking finding came from MRI scans before and after: those with improved fitness had an increase in brain volume in the frontal and temporal lobes. Scientists knew that this could happen in the hippocampus, but the suggestion that brain volume increased in the cortex was “out there,” in the estimation of neuroscientist Carl Cotman, the researcher who pinpointed the link between exercise and BDNF. “I’m sure he’s right,” Cotman says of Kramer. “He’s a very honest, accurate guy. But the findings are definitely on the outer fringe. I mean, I don’t think anybody with animal studies has shown that a brain region in an older animal gets bigger from a very short period of physical activity.”

It remains to be seen whether Kramer’s findings can be replicated, but the idea that just six months of exercise remodels these crucial areas of the brain is incredibly heartening. In the scans, the exercisers’ brains looked as if they were two to three years younger than they were. The resolution of the images doesn’t show specifically what composed the growth, but given what we know from animal studies, Kramer has his suspicions. “It could be new vascular structure, new neurons, new neuronal connections,” he says. “I think it’s probably all of the above.”

The major implication is that exercise not only keeps the brain from rotting, but it also reverses the cell deterioration associated with aging. More than likely, what Kramer’s scans show is how exercise improves the brain’s ability to compensate. “Let’s say the prefrontal cortex isn’t functioning quite up to par,” he explains. “You might be able to recruit other areas of the cortex to do the task in a different way. One way to think about the increased volume is that it might turn back the clock in terms of how well the circuits function to do different things.”

There’s an awful lot our brains can do with an extra two to three years.

EMOTIONAL DECLINE

It’s no wonder that some people get cranky with old age. It’s a time often marked by loss — of career, relationships, possibilities, purpose, resilience, courage, and vitality. Depression can come out of nowhere, and it’s an important issue for older adults because it increases the risk for dementia. The hormones estrogen, in women, and testosterone, in men, decrease with age, and this can lead to a shift in mood or a loss of vigor and interest. Also, one of the reasons depression is a risk factor for dementia is that it has corrosive effects on the hippocampus: if we’re under constant stress and the hormone cortisol stays elevated, it eats away at our synapses. Since aging neurons are less resistant to the effects of stress to begin with, this is really something to guard against or, better yet, to attack proactively.

As we get older and our bodies weaken and our energy levels decline, we might be reluctant to take on challenges such as that trek in Nepal or even the local bridge tournament. But challenges are important because they boost our resilience.

I think back to my mom, who was so vibrant and involved until she broke her hip. It seemed that she became even more daring with age, and instead of turning down novel experiences she would respond with, “Why not!?” As a small example, one night while she was visiting, we were talking about eating at a fancy new Thai restaurant, and I dismissed the idea as quickly as I had mentioned it, assuming my mom wouldn’t like it. She must’ve been about eighty at the time, and I couldn’t picture her digging into a plate of exotic cuisine that looked like architecture. But she said, “Let’s go! I want to try it.” It makes me chuckle to this day, picturing her face when she sampled my curry dish — the spiciest food she’d ever tasted. She loved her coconut soup, though, and we laughed all the way through dinner.

Exercise is obviously a great way to challenge yourself and your brain, and all the better if it puts you in contact with other people and gets you out and about. Consider a recent study from the Rush Alzheimer’s Disease Center. It showed that people who feel lonely — those who identify with statements such as “I miss having people around” and “I experience a general sense of emptiness” — are twice as likely to develop Alzheimer’s. And it’s clear from the studies at Duke University that exercise reduces depression and is even better than Zoloft at keeping people from relapsing.

A particularly important effect of exercise for older adults is that it rallies dopamine, which diminishes with age. This is a critical neurotransmitter in the context of aging because it’s the major signal bearer of the reward and motivation systems. Apathy can become a defining characteristic for older folks, and it’s particularly important to watch for when people move into retirement communities and nursing homes. Even in the best and homiest facilities, depression and a lack of motivation can set in as people feel they’re just waiting to die.

I’m familiar with one retirement home that’s doing something about this problem by trying to get the residents involved and interested in exercise. University Living, in Ann Arbor, Michigan, has a fitness center with aerobic and strength-training machines designed to accommodate people who aren’t so agile anymore, even those who use walkers to get around. The gym is called Preservation Station. And they’ve hired an exercise physiologist who specializes in aging to run group classes and serve as a personal trainer for the able-bodied among their seventy residents. But a lot of what June Smedley does in her role as fitness director is knock on doors and entreat people to work out. “Boy, they get mad at me sometimes!” Smedley says. “They’ll chase you out of their rooms.” Most of her prospective trainees are eighty-somethings who didn’t grow up with the notion that exercise is inherently healthy, and she says the motivation to participate is pretty low. “A lot of them are depressed, and that just drives their whole mentality,” she says. “Their favorite thing to do is just go and sit.”

One of her exercise poster boys is an eighty-year-old former engineer — I’ll call him Harold — who lives there because his wife has Alzheimer’s and needs daily care. He works out five days a week, doing a full regimen that includes a ten-minute warm-up, a round on the weight machine, balance drills on the physioball, and then a thirty-minute aerobic workout on the NuStep, a sort of recumbent stair climber with arm levers.

“I don’t make a career out of it,” says Harold, “but my primary motivation is to be able to do the things I enjoy doing.” That means skiing in the winter and playing golf in the summer, when he walks eighteen holes twice a week. Six months after his eightieth birthday, Harold went skiing for a week in Utah with friends, in keeping with a fifteen-year tradition. He says the core strengthening he’d been doing with June helped his stamina and his form. He was able to ski nonstop from the top of Alta, at 10,550 feet, to the bottom — a descent of about 2,000 feet in elevation that would be difficult for any flatlander. In addition to keeping him on the slopes, his routine has helped him manage the strain of tending to his wife. “Even though there’s good health care here, I still have a lot of husbandly duties,” he says. “I think exercise reduces the stress. I always work up a pretty good sweat, and it gives me something to look forward to each day. And time for myself. I feel a sense of accomplishment. There’s no question that it’s helpful for my mental and emotional and physical well-being.”

DEMENTIA

Dementia is a loss of function that dramatically undermines our ability to get through daily life. It happens when a particular area of the brain is impaired or shuts down, not unlike when a fuse gets blown in a home’s circuit breaker: the kitchen appliances may work fine, but the lights in the bedroom have gone dark.

There are different types of dementia, depending on which circuit is down, and what tripped it. The most common form, by far, is Alzheimer’s disease, which is marked by inflammation and the buildup of amyloid plaque that begins in the hippocampus and spreads to the frontal and temporal lobes, as well as intracellular waste called neurofibrillary tangles. According to the 2000 census, about 4.5 million Americans have Alzheimer’s, and that number is expected to triple, to more than 13.2 million, over the next fifty years as baby boomers enter old age.

Stroke stems from a collapse or rupture or blockage of capillaries anywhere in the brain. If the blood flow is cut off to the temporal lobe — the brain’s dictionary — you can speak but you can’t get the words right. If you have a stroke in the frontal cortex, you won’t be able to speak, but you can understand what people are saying to you.

The next most common form of dementia is Parkinson’s disease, in which the dopamine neurons in the subtantia nigra get depleted and cut off the flow of the neurotransmitter to the basal ganglia, which is the brain’s automatic transmission. The basal ganglia is necessary to smoothly shift between mental or physical tasks and start and stop motor movements; when dopamine runs dry, it’s as if the transmission fluid has been drained, thus the classic tremors of Parkinson’s. The disease typically comes on later in life and afflicts about 1 percent of the population over age sixty. (Early-onset cases like that of Michael J. Fox are rare.) The motor impairments show up first and are followed by mental ones, such as depression, attention problems, and, ultimately, dementia.

The biggest risk factor for dementia is the set of genes we’re born with. There are a number of genes related to Alzheimer’s, such as the apolipoprotein (Apo) E4 variation, but it’s important to remember that having a certain gene doesn’t necessarily predetermine our fate. The ApoE4 variation, for instance, is present in approximately 40 percent of Alzheimer’s patients, but 30 percent of the general population (unafflicted by the disease) carries it too. And there are plenty of Alzheimer’s patients who do not have the ApoE4 variation. Genes determine our risk for a disease, but our lifestyle and environment can either trigger or suppress those risks. One study, for example, showed that our chances for developing Alzheimer’s drops 17 percent for every year of education we have beyond high school.

Statistics aside, we know from animal studies that exercise can redirect the biology of the brain. Carl Cotman tested the effects of exercise on mice bred with a gene predisposing them to plaque buildup and found that exercise slowed down the accumulation compared to the inactive mice. Exercise also prevents inflammation, which Cotman believes might trigger the plaque accumulation — inflammation increases in the transition stage from cognitive decline to Alzheimer’s.

Mattson found the same sort of result in rats that had their dopamine neurons knocked out to mimic the biology of Parkinson’s. The brains of animals allowed to run on wheels showed better plasticity and more connections in the basal ganglia, suggesting that they had adapted by building up circuits to compensate for the dopamine decline.

But our knowledge of what exercise does for Parkinson’s, in particular, extends far beyond lab rats. Over the past five or ten years, exercise has been used more and more as a treatment, particularly in the early stages of the disease. Researchers started testing the effects of exercise because it calls into action the motor area that degenerates in Parkinson’s; stimulating the basal ganglia through exercise increases the connections and boosts BDNF and other neuroprotective factors. One study looked at the effects of using exercise in combination with levodopa (L-dopa), the common drug treatment for Parkinson’s and a dopamine precursor that increases production of the neurotransmitter. The problem with L-dopa is that it loses effectiveness over time (and it has many side effects). Doing forty minutes of easy stationary cycling immediately before taking L-dopa improved the effectiveness of the medicine on motor function.

And while researchers can’t say exactly how exercise counteracts the effects of Alzheimer’s — they’re still trying to figure out what causes the disease — Cotman believes that reducing inflammation and boosting neurotrophic factors are likely explanations.

Population studies support the evidence that exercise holds off dementia. In one, about fifteen hundred people from Finland originally surveyed in the early 1970s were contacted again twenty-one years later, when they were between sixty-five and seventy-nine years old. Those who had exercised at least twice a week were 50 percent less likely to have dementia. What’s particularly interesting is that the relationship between regular activity and the onset of dementia was even more pronounced among those carrying the ApoE4 gene. The researchers suggest that one explanation might be that their brains’ neuroprotective systems are naturally compromised by the gene variant, making lifestyle particularly important. The bottom line, as Mattson says, is that “all we can do at the present time is modify the environmental factors to get the best out of whatever genes we have.”

THE LIFE LIST

Much of the public discourse on aging focuses on baby boomers becoming senior citizens and the belief that their vast numbers will take an unprecedented toll on the health care system, in the form of dementia and other costly health problems. But I don’t believe we’re stuck with this picture of doom and gloom. Despite my generation’s familiarity with fast food and pay per view, we also came of age with Kenneth Cooper’s revolutionary concept of aerobics. Unlike previous generations, we recognize how a healthy heart and healthy lungs stave off disease, and we know our way around the gym. My mother just happened to have the good habit of walking, and even Harold, the eighty-year-old skier from Michigan, isn’t terribly well versed in matters of health and fitness. He once asked the trainer June Smedley what was causing a muscle twitch, and when she suggested it might be dehydration, he scoffed, saying, “I drink lots of fluids — coffee, milk, and wine!”

I have faith that when people come to recognize how their lifestyle can improve their health span — living better, not simply longer — they will, at the very least, be more inclined to stay active. And when they come to accept that exercise is as important for the brain as it is for the heart, they’ll commit to it. Here’s how exercise keeps you going:

1. It strengthens the cardiovascular system. A strong heart and lungs reduce resting blood pressure. The result is less strain on the vessels in the body and the brain. There are a number of mechanisms at work here. First, contracting muscles during exercise releases growth factors such as VEGF and fibroblast growth factor (FGF-2). Aside from their role in helping neurons bind and promoting neurogenesis, they trigger a molecular chain reaction that produces endothelial cells, which make up the inner lining of blood vessels and thus are important for building new ones. These inroads expand the vascular network, bringing each area of the brain that much closer to a lifeline and creating redundant circulation routes that protect against future blockages. Second, exercise introduces more nitric oxide, a gas that widens the vessels’ passageways to boost blood volume. Third, the increased blood flow during moderate to intense activity reduces hardening of the brain arteries. Finally, exercise can to some extent counteract vascular damage. Stroke victims and even Alzheimer’s patients who participate in aerobic exercise improve their scores on cognitive tests. Starting when you’re young is best, but it’s never too late.

2. It regulates fuel. Researchers at the Karolinska Institute conducted a nine-year study of 1,173 people over age seventy-five. None of them had diabetes, but those with high glucose levels were 77 percent more likely to develop Alzheimer’s.

As we age, insulin levels drop and glucose has a harder time getting into the cells to fuel them. Then glucose can skyrocket, which creates waste products in the cells — such as free radicals — and damages blood vessels, putting us at risk for stroke and Alzheimer’s. When everything is balanced, insulin works against the buildup of amyloid plaque, but too much encourages the buildup, as well as inflammation, damaging surrounding neurons.

Exercise increases levels of insulin-like growth factor (IGF-1), which regulates insulin in the body and improves synaptic plasticity in the brain. By drawing down surplus fuel, exercise also bolsters our supply of BDNF, which is reduced by high glucose.

3. It reduces obesity. Aside from wreaking havoc on the cardiovascular and metabolic systems, body fat has its own nasty effects on the brain. The CDC estimates that 73 percent of Americans over sixty-five are overweight, and, given the potential problems obesity can lead to — from cardiovascular disease to diabetes — the agency is right in declaring it a pandemic. Simply being overweight doubles the chances of developing dementia, and if we factor in high blood pressure and high cholesterol — symptoms that often come along with obesity — the risk increases sixfold. When people retire, they figure they deserve a break after working their whole lives, and they start piling on the food. But what they don’t realize is that having dessert with every meal is no treat. Exercise, naturally, counteracts obesity on two fronts: it burns calories, and it reduces appetite.

4. It elevates your stress threshold. Exercise combats the corrosive effects of too much cortisol, a product of chronic stress that can bring on depression and dementia. It also bolsters neurons against excess glucose, free radicals, and the excitatory neurotransmitter glutamate, all necessary, but they can damage cells if left unchecked. Waste accumulates and junks up the cellular machinery, and it starts turning out dangerous products — damaged proteins and broken fragments of DNA that trigger the latent and ultimately inevitable process of cell death that defines aging. Exercise makes proteins that fix the damage and delay the process.

5. It lifts your mood. More neurotransmitters, neurotrophins, and connectivity shore up the hippocampus against the atrophy associated with depression and anxiety. And a number of studies have shown that keeping our mood up reduces our chances of developing dementia. The evidence applies not only to clinical depression but also to general attitude. Staying mobile also allows us to stay involved, keep up with people, and make new friends; social connections are important in elevating and sustaining mood.

6. It boosts the immune system. Stress and age depress the immune response, and exercise strengthens it directly in two important ways. First, even moderate activity levels rally the immune system’s antibodies and lymphocytes, which you probably know as T cells. Antibodies attack bacterial and viral infections, and having more T cells makes the body more alert to the development of conditions such as cancer. Population studies bear this out: The most consistent risk factor for cancer is lack of activity. Those who are physically active, for instance, have a 50 percent lower chance of developing colon cancer.

Second, part of the immune system’s job is to activate cells that fix damaged tissue. When it’s out of whack, these damaged spots fester, and you’re left with chronic inflammation. This is why, if you’re over fifty, your blood will be tested for C-reactive proteins as part of your standard physical. These proteins are a sign of chronic inflammation, a primary risk factor for cardiovascular disease and Alzheimer’s. Exercise brings the immune system back into equilibrium so it can stop inflammation and combat disease.

7. It fortifies your bones. Osteoporosis doesn’t have much to do with the brain, but it’s important to mention because you need a strong carriage to continue exercising as you age, and it is a largely preventable disease.

Osteoporosis afflicts twenty million women and two million men in this country. More women every year die from hip fractures — a vulnerability of osteoporosis — than from breast cancer. Women reach peak bone mass at around thirty, and after that they lose about 1 percent a year until menopause, when the pace doubles. The result is that by age sixty, about 30 percent of a woman’s bone mass has disappeared. Unless, that is, she takes calcium and vitamin D (which comes free with ten minutes of morning sun a day) and does some form of exercise or strength training to stress the bones. Walking doesn’t quite do the job — save that for later in life. But as a young adult, weight training or any sport that involves running or jumping will counteract the natural loss. The degree to which you can prevent the loss is impressive: one study found that women can double their leg strength in just a few months of weight training. Even women in their nineties can improve their strength and prevent this heartbreaking disease.

8. It boosts motivation. The road to successful aging really begins with desire, because without the desire to stay engaged and active and alive, people quickly fall into the death trap of being sedentary and solitary. One of the problems of getting older is the lack of challenges, but with exercise we can continually improve and push ourselves.

Exercise counteracts the natural decline of dopamine, the key neurotransmitter in the motivation and motor systems. When you move, you’re inherently boosting motivation by strengthening the connections between dopamine neurons, while at the same time guarding against Parkinson’s. This really underscores the idea that if you’re not busy living, your body will be busy dying. It’s important to have plans and goals and appointments, and this is why sports such as golf and tennis are great. They require constant self-monitoring and the motivation to improve.

9. It fosters neuroplasticity. The best way to guard against neurodegenerative diseases is to build a strong brain. Aerobic exercise accomplishes this by strengthening connections between your brain cells, creating more synapses to expand the web of connections, and spurring newly born stem cells to divide and become functional neurons in the hippocampus. Moving the body keeps the brain growing by elevating the supply of neurotrophic factors necessary for neuroplasticity and neurogenesis, which would otherwise naturally diminish with age. Contracting your muscles releases factors such as VEGF, FGF-2, and IGF-1 that make their way from the body into the brain and aid in the process. All these structural changes improve your brain’s ability to learn and remember, execute higher thought processes, and manage your emotions. The more robust the connections, the better prepared your brain will be to handle any damage it might experience.

LISTEN TO MY MOTHER

My family got its first television when I was about eight, but we never camped out in front of it. We weren’t allowed to; my mom would say, “Don’t just sit there; go out and play.” We ate fish every week, not only because we were Catholic, but also because even back then it was known as “brain food.” And the nuns at school drilled in the importance of staying mentally active with the mantra “An idle mind is the devil’s workshop.” Long before the benefit of scientific proof, the stern women of my upbringing fixated on the three pillars of a healthy lifestyle: diet, exercise, and staying mentally active. In that sense, the prescription for living a long and rich life hasn’t changed much. But now we know so much more about the why and how that it’s hard to ignore the advice.

DIET: EAT LIGHT, EAT RIGHT

The one proven way to live longer is to consume fewer calories — at least if you’re a lab rat. In experiments in which rodents eat 30 percent fewer calories, they live up to 40 percent longer than animals allowed to eat as much as they want. “Our control group is really overfed and underexercised,” says neuroscientist Mark Mattson, pointing out that group is “a good match for a lot of the American population.” A study in monkeys that began eighteen years ago in the experimental gerontology lab at the National Institute on Aging suggests the same holds true in primates. And one human trial showed that asthma patients on a restricted diet for two months — three meals one day and only five hundred calories the next — had fewer markers of oxidative stress and inflammation in their blood (and their asthma symptoms improved). This finding supports the theory that imposing mild stress on the cells — in this case depriving them of fuel — makes them more resilient to future challenges and reduces free radicals. “It’s kind of like exercising for an hour every day,” Mattson says. “It’s a mild stress, but as long as there’s a recovery period, it’s good.”

He is cautious about telling people to skip meals, but that’s what he does: no breakfast, a salad for lunch, and a normal dinner, for a total of about two thousand calories. It’s likely that people of normal weight wouldn’t benefit as much, and anyone over fifty should be careful about malnourishment because they’re losing muscle and bone anyway. But if you’re overweight, you’re inflicting damage to your brain.

As for what you do eat, there are certain foods that activate cellular repair mechanisms, as I mentioned in chapter 3. Cumin, garlic, onions, and broccoli, for instance, all contain toxins meant to keep pests at bay, but the levels are low enough that they trigger a beneficial stress response. The same holds true for free radical–fighting foods such as blueberries, pomegranates, spinach, and beets — it’s the toxins as well as the antioxidants that ultimately lead to cellular repair. Green tea and red wine are beneficial in the same way.

The rest of your plate should be balanced with whole grains, proteins, and dietary fats. Low-carb diets may help you lose weight, but they’re not good for your brain. Whole grains have complex carbohydrates that supply a steady flow of energy rather than the spike and crash of simple sugars, and they’re necessary to transport amino acids such as tryptophan into the brain. As you learned in chapter 4, tryptophan is a precursor necessary for the production of serotonin, and it and other important amino acids come from protein.

The brain is made up of more than 50 percent fat, so fats are important too, as long as they’re the right kind. Trans fat, animal fat, and hydrogenated oils gum up the works, but the omega-3s found in fish are enormously beneficial. Population studies have shown that countries in which people eat a lot of fish have lower incidence of bipolar disorder. And some people use omega-3s as a stand-alone treatment for mood disorders and ADHD. One study showed that people who eat fish once a week slow the yearly rate of cognitive decline by 10 percent. The Framingham Heart Study followed nine hundred people for nine years and found that those who ate three meals with fish oil per week were half as likely to develop dementia. Omega-3s lower blood pressure, cholesterol, and neuronal inflammation, and they elevate the immune response and BDNF levels. You can find omega-3s in deep-water fish such as salmon, cod, and tuna, or you can take a daily supplement that contains 1200 mg of eicosapentaenoic acid (EPA) and 200 mg of docosahexaenoic acid (DHA) — the two key omegas.

Vitamin D is being recognized not only for its importance in strengthening bones but also as a measure against cancer and Parkinson’s. I would recommend 1000 IU (international units) of vitamin D and for women, 1500 mg of calcium. I would also recommend taking vitamin B with at least 800 mg of folate, which improves memory and processing speed.

PHYSICAL EXERCISE: STEADY DOES IT

For anyone over sixty, I recommend exercising almost every day. In retirement, why not? Six days a week would be ideal, but make it fun rather than work. It’s a good idea to use a heart rate monitor. They’re invaluable for keeping track of your progress, and this is both motivating and reassuring. You’re not left wondering whether you’ve done enough, at the proper intensity. They come with instructions, but essentially you subtract your age from 220 to find your theoretical maximum heart rate, and then use that number to figure out how hard you should be working. (I’ll explain more about using them in the next chapter.)

Your overall strategy should include four areas: aerobic capacity, strength, and balance and flexibility. You should consult with a doctor or trainer who knows your history, but I can give you some solid guidelines.

Aerobic. Exercise four days a week, varying from thirty minutes to an hour, at 60 to 65 percent of your maximum heart rate. At this level, you’ll be burning fat in the body and generating the ingredients necessary for all the structural changes in the brain I’ve discussed. Walking should be perfectly adequate, but do it outside with a friend if possible. Whatever you choose, try to find something that you will enjoy over the long haul. Try a more intense pace for two days a week — 70 to 75 percent of your maximum — for twenty to thirty minutes. If you haven’t been exercising, you’ll want to build up to this speed, and that’s fine. Consistency is probably more important than intensity. “You don’t have to work as hard as you may think you do,” suggests Kramer. “If you can work harder and run rather than walk, that’s great. But if you can’t, walking is what we’ve looked at, and it can have some fairly dramatic effects.”

Strength. Hit the weights or resistance machines twice a week, doing three sets of your exercises at weights that allows you to do ten to fifteen repetitions in each set. This is critical for preventing and counteracting osteoporosis: even if you do all the aerobic training in the world, your muscles and bones will still atrophy with age. A Tufts University study of women fifty to seventy years old showed that those who participated in strength training for a year added 1 percent of bone density in their hips and spine, while the sedentary group lost 2.5 percent of the density in those areas. If you don’t have experience with resistance training, it’s a great idea to get a trainer for the first month or to find some type of instruction — good form is important in avoiding injuries. Activities that involve bouncing or jumping also help strengthen your bones: tennis, dancing, aerobics class, jumping rope, basketball, and, of course, running.

Balance and Flexibility. Focus on these abilities twice a week for thirty minutes or so. Yoga, Pilates, tai chi, martial arts, and dance all involve these skills, which are important to staying agile. Without balance and flexibility, your ability to stick with an aerobic and strength-training regimen will diminish. In lieu of an activity, you can do drills on an exercise ball, balance board, or Bosu, which is half a rubber ball that you stand on to challenge your core muscles. Remember Harold, the octogenarian skier? He trained on the Bosu for his most recent ski trip.

MENTAL EXERCISE: KEEP LEARNING

My advice here is to keep challenging your mind. You know by now that exercise prepares your neurons to connect, while mental stimulation allows your brain to capitalize on that readiness. It’s no coincidence that study after study shows that the more education you have, the more likely you are to hang onto your cognitive abilities and stave off dementia. But it’s not necessarily about the diploma. It’s just that those who have spent a lot of time in school are more likely to remain interested in learning. Tucked within those statistics are plenty of people who didn’t go to college yet nurture intense interests in the world around them. The most inspiring evidence of this comes from an urban health study called Experience Corps conducted by epidemiologists at Johns Hopkins University. They enlisted 128 predominantly African American women between sixty and eighty-six with low education levels and socioeconomic status and trained them to teach grade school children reading skills, library skills, and so on. Not only did the children improve their scores on standardized tests, but the health of the volunteers substantially increased: half of the women who were using canes stopped; 44 percent reported feeling stronger; the amount of time they spent watching television dropped 4 percent; and they reported a significant increase in the number of people they could turn to for help.

Volunteering is beneficial because it involves social contact, which is inherently challenging for the brain. Anything that keeps you in contact with other people helps you live better and longer — statistics show a tight inverse relationship between sociability and mortality. Novel experiences demand more from your brain, and this builds its ability to compensate. You get more Miracle-Gro, more connections, more neurons, and more possibilities.

There was a nun named Sister Bernadette who died of a heart attack at age eighty-five in the mid-1990s. Along with more than six hundred other nuns, she donated her brain to science as part of an ongoing study conducted by epidemiologist David Snowdon, who memorialized the School Sisters of Notre Dame, in Mankato, Minnesota, in his inspiring book, Aging with Grace. The nuns constantly challenge their minds, with vocabulary quizzes, mental puzzles, and debates about public issues, and many of them live to be one hundred or more. The interesting thing about Sister Bernadette is that she scored in the ninetieth percentile on cognitive tests right up until she died, but when her brain was examined postmortem, it showed massive damage from Alzheimer’s disease. Tissue from her hippocampus to her cortex was riddled with plaque and neurofibrillary tangles to the most extensive degree, and she also carried the ApoE4 gene variant. In other words, she should have been utterly lost to the ravages of dementia. Yet despite the damage in her brain, she remained mentally sharp.

Snowdon points to the notion of cognitive reserve as a possible explanation. This is the brain’s ability to adapt and compensate for damage by recruiting other areas to help with tasks. By teaching until a late age and staying mentally active, Sister Bernadette almost certainly trained her brain to work around the genetic hand she was dealt. Her example, like that of my mother, is one to live by.