Successful Aging: A Neuroscientist Explores the Power and Potential of Our Lives

by Daniel J. Levitin

It turns out that the primary cause of confusion, disorientation, and delirium among older adults is not Alzheimer’s disease—it’s adverse effects from medications or from drug interactions. There are a number of cases of older adults being shunted off to an old age home not because they have become mentally incapacitated, as well-intentioned family and friends might think, but because of polypharmaceutical complications.

circadian cycles are advanced in older adults who tend to go to sleep earlier and wake earlier. Such age-related variation also may have been an evolutionary adaptation: It might have been a survival advantage for the older people, whose hunting skills had diminished, to stand on guard at night so that the younger, sharper hunters could get a good night’s sleep. This has led one group of researchers to propose the “poorly sleeping grandparent hypothesis.” If the sentinel hypothesis is true, we’d predict that in ancient times, only rarely would all members of a living group be asleep at the same time. Alternatively, if all individuals were asleep at the same time, it would discredit the sentinel hypothesis.

Older adults tend to experience a shift in their chronobiological cycles (see figure on the previous page) called a phase advance; as they age, people are more likely to become morning types as they age.

There are time-of-day effects for alertness and performance that become starkly emphasized when we age. Adults after the age of sixty or so begin to show performance differences on a range of neuropsychological tests—memory, problem solving, spatial intelligence, reasoning, fine motor coordination, and athletic performance. Test them in the morning and they are normal; test them in the mid- to late afternoon and they show reduced performance, compared to forty- or fifty-year-olds (as we saw in Chapter 4, on the problem-solving brain). The differences become even more pronounced after age seventy. Give a standard memory test in the morning and they appear fine. But after noon, the decrements can be large. The take-home message is this: Make important decisions, those about finances, health, and the like, before noon. Your thinking is better.

Repetitive disturbances of the circadian rhythm, particularly from frequent time-zone shifts and irregular exposure to light, have now been implicated in a variety of diseases, including metabolic syndrome, immune deficiencies, bone and muscle weakness, cardiovascular disease, cancer, and a shortened life span. Sundowner’s syndrome, the tendency for people with Alzheimer’s disease to show confusion and poor memory in the early-evening hours, may well be the result of circadian rhythm disturbances—patients who can successfully restore a normal sleep-wake pattern can stay longer with their families and postpone the need to be housed in special care facilities.

Generally, it takes your body one day of recovery or planning per one hour of time-zone shift when traveling east, and half a day per one hour of time-zone shift when traveling west. This is a best case scenario. As you get older, it may well take longer.

For most people, the sleep-wake cycle creates an energy dip between two and four A.M. (when they’re asleep) and another one between about one and three P.M. (postlunch). If you’re sleep-deprived—which refers not just to the amount of sleep you’ve gotten over the past few days but also to the quality of that sleep—you will tend to notice the postlunch dip more. And you’ll notice it more as you age.

Melatonin levels tend to rise about fourteen hours after waking. If you get eight hours’ sleep every night and wake at six A.M., that means your melatonin levels will naturally rise around eight P.M., and you’ll start to get sleepy and go to bed two hours after that, around ten P.M. If it takes about an hour for a melatonin pill to be absorbed into your bloodstream, that means taking one about three hours before bedtime. The next most effective treatment, after light therapy and melatonin, is moderate late-afternoon or early-evening exercise, like going outside for a walk. The combination of all three is the best.

health span versus disease span—the amount of time you are able to avoid declining health and live a fully productive, self-sufficient life. There’s a parallel concept called productivity span that can apply not just to the arc of your life but also to the arc of a single day: There are times of day when you are at your best and other times when you are not. I mentioned this earlier in the discussion of chronotypes and the fact that older adults tend to perform better in the morning (whenever that subjective morning is—the first six hours of being awake).

peak performance in grip strength, running, jumping, oxygen uptake, and muscle function tends to occur between four P.M. and eight P.M. in the athlete’s home time zone.

Is this why football assumes the home team always has the advantage?

The problem here has to do with the economics and logistics of properly applying the scientific method. Most of what we know (or think we know) about foods and health comes from observational studies or samples of convenience, not proper experiments. In observational studies, as the name implies, we simply watch people who have different diets over a period of years and see how they fare. Any differences between groups of people are attributed to the difference in diets. The scientific problem is that people who eat different foods may have other differences as well that we’re not keeping track of: different tendencies to exercise (or not), sleep duration, attitudes toward medicine, hydration, different daily stressors endured. Someone has just lost their job, another just had their first child, another is a heroin addict, another is a professional athlete, and so on and so on. This goes to the core theme of personal psychology and individual differences versus the generalizations neuroscience allows.

When an atom, molecule, or ion has an unpaired electron, it is unstable and is called a free radical. Free radicals are produced all the time as your cells convert glucose to energy. But damage to mitochondria (a subunit of the cell, found inside most cells of your body) can also lead to increased production of free radicals. And so can consuming certain substances, such as fried foods, alcohol, tobacco smoke, pesticides, and air pollutants. Free radicals, because they’re unstable, can cause damage to DNA and cell membranes by grabbing their electrons through a process called oxidation. This easily becomes a chain reaction. One molecule with a free radical grabs the electron from another, leaving it a free radical; then this one grabs the electron from another molecule, leaving it a free radical; and pretty soon the whole thing has snowballed out of control. In the meantime, all of these molecules with free radicals can’t perform their cellular functions properly, and you get oxidative stress.

Oxidative stress is believed to underlie a wide range of diseases, including cancer, diabetes, and neurological disorders such as Parkinson’s and Alzheimer’s disease, and to shorten life span. It causes high LDL levels (low density lipoprotein—the “bad” cholesterol) and the accumulation of plaques that can lead to heart disease. It even plays a role in the development of wrinkles. It’s been known since the 1960s that free radicals accelerate the aging process and that the reduction of free radicals can delay aging.

Cholesterol is a waxy substance that circulates in your blood and attaches to proteins there. Your body needs cholesterol to build healthy cells, including brain cells, but high levels of certain forms of cholesterol can increase your risk of heart disease. When cholesterol combines with proteins, the resulting molecule is called a lipoprotein. Low-density lipoprotein (LDL, the “bad” cholesterol) transports cholesterol particles throughout your body. It can build up in the walls of your arteries, making them hard and narrow and causing arteriosclerosis. High-density lipoprotein (HDL, the “good” cholesterol) picks up excess cholesterol and takes it back to your liver, which then removes it from your body.

LDL levels naturally rise with age, making healthy lifestyle habits increasingly important, especially after age fifty.

Diets high in soluble fibers are good because the fiber binds to the LDL cholesterol molecules in the digestive system and drags them out of the body before they get into circulation. Some good sources of soluble fiber are oats (oatmeal, Cheerios, Trader Joe’s O’s), barley and other whole grains, beans (including soy beans and soy milk), high-fiber fruits (apples, strawberries, citrus; the pectin they contain is a soluble fiber), eggplant, okra, fatty fish, liquid vegetable oils, and nuts (just two ounces of nuts a day can lower LDL by 5 percent). Diets high in omega-3 fatty acids, as found in fatty fish, seeds (especially chia, flaxseed, and hemp), nuts (especially walnuts), and olive and canola oils also lower LDL and reduce the risk of heart disease by 7 percent. Insoluble fibers (wheat bran, vegetables, and whole grains) are also healthy because they prevent constipation and diverticulitis.

Ben Franklin advised in Poor Richard’s Almanack, “To lengthen thy life, lessen thy meals.” It’s been known for more than a decade that mice and rats that have a calorie-restricted diet can live 30 to 40 percent longer. When you have easy access to food and nutrients, and your physiological stress levels are low, your genes support cellular growth and reproduction.

Caloric restriction, because of its interaction with the insulin signaling system, appears to be good for the brain. Why might that be? Neuroscientist Mark Mattson at Johns Hopkins University says, “If you’re hungry and haven’t found food, you’d better find food. You don’t want your brain to shut down if you’re hungry.” Some of the neural benefits that are found with fasting also occur with vigorous exercise. The neurochemical changes are similar: Both stimulate the production of brain-derived neurotrophic growth factors (BDNFs). Fasting stimulates the production of ketones, an energy source for neurons. Fasting can increase the number of mitochondria in neurons, which helps them produce more energy.

There’s also emerging evidence that insulin may play a role in developing Alzheimer’s disease. This has led some forward-thinking doctors to prescribe the diabetes medication metformin, a blood sugar–lowering drug, proactively to patients with a family history or other risk factors for Alzheimer’s and dementia.

Vegetable proteins are a part of that balanced diet. You may have read reports that soy products interfere with sex hormones, lowering testosterone in men and leading to estrogen problems in menopausal women. These reports were based on flawed data, and the current thinking is that soy is beneficial for all except those who are allergic to soy.

Dehydration is deadly. It is the second leading killer of children under four worldwide and the eighth leading cause of death among adults over seventy.

Alcohol is also a culprit: It turns off hormones that help us absorb water so we lose more fluids than normal.

Older persons have an increased risk of dehydration, even when water is readily available to them, because thirst detectors in the brain degrade.

Dehydration results from an imbalance of water, salts, and electrolytes in the blood. Electrolytes include sodium, chloride, potassium, and magnesium. Rehydrating does not mean simply drinking more water, because when you’re dehydrated, the body can’t retain the water that you drink and water alone doesn’t replace the depleted salts and electrolytes. Rehydration requires drinking an oral rehydration salts (ORS) solution. An ORS solution is a mixture of water, salt, and sugar; it is absorbed in the small intestine and replaces the water and electrolytes lost in dehydration. If dehydration is accompanied by diarrhea, zinc supplements can reduce the duration of a diarrhea episode by 25 percent. Cases of severe dehydration require intravenous fluids.

For maintaining hydration, limit alcohol intake or drink at least one 8-ounce glass of water for every alcoholic beverage you ingest.

As Hippocrates noted, “It is a general rule that intestines become sluggish with age.” Constipation is one of the most common and annoying problems of aging, affecting 50 percent of older adults. As we age, the intestinal muscles that help move food along weaken and the contractions are not as strong. Often, medications taken by older adults cause constipation as a side effect. Many older adults become less physically active, which also increases constipation. It disproportionately affects women, nonwhites, people from a lower socioeconomic status, and those who suffer from depression.

Bulk-forming laxatives aren’t digested; instead, the fiber they contain allows you to retain more fluid—that’s why you need to be sure that if you use them, you increase your consumption of fluids. The water absorption produces a softer, bulkier stool. The bulky size stimulates the intestinal muscles to contract, causing everything to move along, leading to an easier bowel movement. It can take from twelve to thirty-six hours for bulk-forming laxatives to produce results, so they do not provide immediate relief from constipation—they are best used for ongoing digestive health. Examples include psyllium husks (Metamucil), ground flaxseed, wheat dextrin (Benefiber), methylcellulose (Citrucel), and polycarbophil (FiberCon, Prodiem).

Osmotic laxatives draw water into the bowel from the intestines, thereby softening the stool. They can deplete electrolytes and cause dehydration, and so it’s also important to stay hydrated when taking them. They can work within six hours. Many are polyethylene glycol–based (Lax-A-Day, MiraLAX, PegaLAX, RestoraLAX). Unlike bulk-forming laxatives, osmotic laxatives are intended for short-term, not daily, use, they shouldn’t be taken for more than seven days, and they are habit-forming.

Your digestive system—your gut—has its own computer, known as the enteric nervous system, with half a billion neurons, and containing about 100 trillion bacteria, both good and bad. Collectively they are known as the gut microbiota,

There is an emerging body of evidence that the gut microbiome also affects cognition, behavior, and brain health. This is cutting-edge stuff and the story is still being written. We already know that serotonin is an important neuroregulator of mood, memory, and anxiety. It turns out that 90 percent of the serotonin in the body resides in the gut, and it is manufactured there by bacteria such as Candida, Streptococcus, Escherichia, and Enterococcus.

Gut bacteria have been linked to mental well-being and depression. People who lack two particular bacteria, Coprococcus and Dialister, are more likely to be depressed, and those who have normal levels of them report a higher general quality of life. Coprococcus is associated with dopamine signaling, and it also produces butyrate, a fatty acid that is an important anti-inflammatory agent; increased inflammation has been linked to depressive symptoms.

Early life stressors can also have an influence on the composition of the gut microbiome. That composition is affected by the mother’s diet and stress levels and by travel through the birth canal. Children who are delivered via Caesarean section show a reduced diversity of their gut microbiome. In animals, stress caused by the separation of rhesus monkeys from their mothers changed the microbiota and decreased their Bifidobacterium and Lactobacillus levels. Rats separated from their mothers showed decreased fecal Lactobacillus levels.

A particular problem concerns older adults in long-term-care facilities. The gut microbiome of such individuals shows substantially less diversity than that of older adults who continue to live in the cities, towns, and farms they always lived in. Interacting with a large and diverse number of people (and farm animals) maintains a diverse microbiome. The extremely antiseptic nature of long-term-care facilities, and the restricted pool of inhabitants (mostly older humans), may impoverish the microbiome and reduce its diversity. In a few studies so far, the loss of diverse community-associated microbiota correlates with increased frailty, inflammatory conditions, and even death. An important new frontier in gerontology is going to be modulating the individual’s microbiome with dietary interventions designed to promote healthier aging.

The big problem is that most probiotic formulations can’t survive the acidic environment of the stomach, and if they do, they don’t thrive enough to colonize the gastrointestinal tract.

fecal microbiota transplantation (bacteriotherapy), in which fecal material from a healthy person, which contains beneficial bacteria, is transplanted into the patient in order to restore the normal balance of gut bacteria. Scientists see the potential for treating a range of diseases, including cancer, diabetes, and possibly even Alzheimer’s. The technique has had mixed results and is still experimental.

The key to diet seems to be not what you eat, but what you don’t. The American diet is too high in processed foods, sugar, salt, and red meat. Junk food is addictive—it overstimulates the brain’s reward system, which evolved in an era when fats and sweets were hard to come by.

Ten thousand years ago, humans plus their pets and livestock accounted for about 0.1 percent of the terrestrial vertebrate biomass inhabiting the earth; we now account for 98 percent. Our success is owing in large part to our problem-solving, adaptive, and exploratory brains.

Exercise is important for two reasons. The obvious one is that it oxygenates the blood. The brain runs on oxygenated glucose, carried by hemoglobin in the blood, and a fresh supply of oxygen is good. The nonobvious reason is that our brains, because they were built to navigate in unfamiliar surroundings, don’t do well when they’re not challenged by having to problem solve. Every step you take on a treadmill or elliptical is helping you with the first of these two imperatives—getting your blood oxygenated—but they don’t help your brain to keep its navigational skills and memory systems honed. Every minute you walk on an unpaved trail, whether in a park or in the wilderness, requires you to make hundreds of microadjustments to foot pressure, angle, and pace. These adjustments stimulate the neural circuitry of your brain in the precise way that it evolved to be used. The area that is most stimulated is your hippocampus, that seahorse-shaped structure that is critical to memory formation and retrieval. This is why so many studies show that memory is enhanced by physical activity.

embodied cognition, the idea that physical properties of the human body, particularly the perceptual and motor systems, play an important role in cognition (thinking, problem solving, action planning, and memory). In this way of thinking, the sensation of movement is inextricably bound with knowledge. Embodied cognition is consistent with this book’s developmental cognitive neuroscience approach. It sees humans as embodied, ecologically and genetically embedded social agents who shape and are shaped by their environment. The body influences the mind just as the mind influences the body. Embodied cognition puts intelligence and control out in the body.

A systematic meta-analysis showed that for adults with mild cognitive impairment, exercise had a significant beneficial effect on memory. Adults with mild cognitive impairment have a considerably increased risk of progressing to dementia, and this specific risk is increased by atrophy of the hippocampus. Physical activity may be just as effective as pharmaceutical agents in improving and maintaining memory, as well as global cognition, and delaying the onset of dementia and other neurological diseases such as Alzheimer’s and Parkinson’s.

physical activity is not the same as exercise. It’s moving around, interacting with the environment. As Cicero knew, it is this kind of interaction that “supports the spirits, and keeps the mind in vigor.”

If memory evolved to help us with spatial navigation, the reason that very young children have no memories is because they are not moving around and interacting with the environment very much.

as older adults begin to move and explore less than, say, young or middle-aged adults, those hippocampal-based memory systems might atrophy—use it or lose it, as the professional athletes say. The central role that the hippocampus plays in general, not just in spatial memory, can additionally account for other cognitive impairments often seen in less active older adults—including decrements in reasoning, hand-eye coordination, and problem solving, as well as general cognitive slowing.

As children, we gain a sense of agency and control over the environment through our interactions with it—playing in the sandbox, playing on a jungle gym. We can lose that sense of agency and control if we reduce our interactions with the environment, which can lead to a loss of motivation and confidence in our ability to deal with our environment, setting off a downward spiral. This is particularly a problem for older adults who are already experiencing three kinds of bodily changes that may spur them to interact with the environment less. First is loss of dexterity, which comes from a general slowing down of nerve transmission speed, loss of nerve conductance, and reduction in eye-hand coordination. Second is a loss of motivation, which may be born of isolation and feelings of loneliness. Third is a loss of joy and pleasure at doing things for oneself, partly owing to reductions in the production and uptake of dopamine, the brain’s reward-chemical signaling channels.

“older adults” are those who are manifestly slowing down, physically and mentally, who can’t do many of the things they used to do, and who are discovering that the things they might want to do are becoming constricted by physical and mental limitations.

A large part of the story of people who manage to stay young, in spite of their chronological age, relates to synaptic plasticity—the ability of the brain to make and form new connections. As we’ve seen, plasticity is influenced by your genetic makeup, your lifetime of experiences, and the culture in which you live. It is also influenced by your daily routines, especially as you get older. The act of transmitting information across synapses, and the forming of new synaptic connections, requires a dramatic increase in the amount of energy used in the brain. Astrocytes, a type of brain cell, serve as suppliers of that energy. A mounting body of evidence shows that physical activity increases the effectiveness of astrocytes and thereby enhances synaptic plasticity, memory, and overall cognition.

observed improvement in memory for human adults who engage in aerobic physical activity. Most effective is to engage in aerobic exercise just before learning something new. When you get your heart rate up just before a mental task, you prime the brain with increased blood flow, which creates an enriched setting for mental activity.

aerobic activity as “any activity that uses large muscle groups, can be maintained continuously and is rhythmic in nature.” It includes swimming, cycling, running, dancing, and walking. It’s called aerobic because aerobic means “living in the presence of oxygen,” and these activities leverage the body’s ability to use oxygen to extract energy from carbohydrates, amino acids, and fat. The ACSM defines anaerobic activity as “physical activity of very short duration, fueled by the energy sources within the contracting muscles and independent of the use of inhaled oxygen as an energy source.” It includes things like strength (weight) training and short-distance running.

Sarcopenia is the loss of muscle tissue—similar to what osteoporosis is for bone. It is a leading contributor to functional decline and loss of independence in older adults.

Movement activities are particularly helpful, indeed essential, for individuals who have a cluster of conditions called metabolic syndrome—increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels—which substantially increases the risk of heart disease, stroke, and diabetes.