Our maximum potential life span as a species is thought to be about 115 years, but many people die before the age of 80 after suffering from an average of three diseases. So we have 35 extra years that we can realize, like some of our centenarians have, and we are beginning to understand how to scientifically capture those years and make them healthy. I’m on a mission to make this happen as soon as possible, and my hope is that this book will encourage people of all ages to support this mission, along with many more researchers and investors. Ideally, we can lengthen life span and also shorten the amount of time that people are sick at the end of their lives. The Centers for Disease Control and Prevention confirmed our findings when they compared the medical costs of the last two years of life for people who die after the age of one hundred with the costs for people who die around age seventy. The centenarians’ costs were a third of the costs for those who died younger. This is good for individuals, families, and entire countries, and in the United States, it can help to significantly lower medical costs as discussed in chapter 7. We are ushering in a future where the norm will be for people to be healthy, active, and mentally sharp during the last quarter of their lives. And fortunately, there’s no need to wait for the new drugs—there are many things you can do right now to slow the aging process and stay healthy, strong, and sharp.
But before we get into recommendations, let me explain my thinking and my limitations. First, the only recommendations that I can safely make are based on data that is derived from clinical controlled studies. The reason these are the only studies I totally trust is because the relationship between the mind and the body affects our health and can also affect the outcome of association studies. When the participants in an association study experience improvements, we don’t know whether it’s because of the treatment, because of something else they’re doing, or because of the placebo effect. We’ve learned that when someone takes a drug or undergoes a treatment that they believe can help them, they are up to 40 percent likelier to show some improvements. So the mind can work for us, but it can also work against us because people who are depressed tend to die earlier than people who aren’t, and there’s biology behind that. Endorphins, proteins, and many other substances that are being secreted from the body and the brain affect our physical and mental health.
With clinical studies, researchers must be able to demonstrate that the intervention being used produces a statistically significant effect. But there aren’t many clinical trials about longevity and the relationship to death as an end point of aging that involve human participants. So I’m also including results from some credible association studies, but not as recommendations—simply as information. It’s important for me to make this distinction because the first rule we learn in medical school is “First, do no harm,” or in Latin, Primum non nocere. So when we conduct a controlled clinical trial, we are not just looking for potential improvements—we are also looking at the side effects. In other words, what are we giving up for whatever we’re gaining? In addition to that, we have established that what’s good for one person can be bad for another, not just because of gender and age differences but also because of simple case-by-case differences—we’re all biologically unique. But there is information that comes out of well-done association studies that can be useful, and I believe there are things that affect our health and longevity that we can’t yet measure, so the jury is still out on many of the innovative ideas being tested. But when I hear stories about people taking treatments, drugs, or botanicals that have not been proved to be safe in clinical trials, I am dismayed by the lack of judgment. Even seemingly innocuous supplements can interact with medications in deleterious ways.
When we medical residents followed Dr. Bar Hama on rounds, he routinely asked us if we thought the patient looked older or younger than his or her age. We quickly realized that biological age and chronological age are not the same. But the impact of this realization didn’t hit home for me until I watched my mother appear to age twenty years over the span of just one. When she was fifty-five, she was diagnosed with acute hemorrhagic pancreatitis and spent three months in the intensive care unit. I was thirty-four at the time, and many nights as I sat by her bed, I was afraid she would die. Her pulse was weak, she had almost no blood pressure, and her oxygen levels were barely detectable. She underwent several surgeries, including the removal of parts of her pancreas and a colostomy. While the colostomy was reversed a year later and she was able to return home, she was more like a seventy-year-old woman than a woman in her late fifties. As a Holocaust survivor, though, she was strong and motivated, and she managed to live to seventy-eight. But the last two decades of her life were wrought with medical problems and her quality of life was not good, even though we all did everything we could for her. For me, this experience drove home the critical importance of extending health span along with life span. And it also exemplified that chronological age and biological age are often not in sync.
To assess people based on biological age, scientists have been trying to agree on a standardized set of aging biomarkers. We’ve done all sorts of tests, from functional—can he get up out of the chair without using his hands and arms?—to biological—what’s his HDL, and how long are his telomeres?—but nothing has proved to be an accurate marker for everyone. We’re finally making some headway, though, as a result of getting large amounts of data and using augmented intelligence.
The FDA supports this move because biomarkers will allow us to treat people based on their biological age instead of their chronological age. This could mean, for example, that if your age is fifty but your biomarkers show that you’re biologically closer to forty-five, you could wait five more years before having your first colonoscopy. The biomarkers will help us to deliver better health care because we will have better ways to predict who is at risk now and who will be at risk later.
Adding to this challenge is that we geroscientists want to find biomarkers that we can change by interfering with the hallmarks of aging. For example, if we administer a new drug or treatment, we want to see that the person’s biological age becomes younger as a result, and this is a tall order. For now, it seems that the best biomarker we have for differentiating between biological and chronological age is the mechanism called methylation. Interaction between the environment and the genome—epigenetics—causes changes in methylation across our genome, which modulates the activity of genes. My friends Steve Horvath and Morgan Levine, scientists at UCLA, measured several hundred methylation sites across the genome, and they are determining chronological age from a blood test. On a population level, what we see in the blood is the same as what we see in the organs. But for individuals, it may be that the biological age of one organ is different from the age of another—the biological age of your heart may be different from the age of your liver. If your heart is older, you may get cardiovascular disease. If your liver is older, you may get liver disease. And for the sake of showing how complex all of this is, adult women’s breasts are biologically ten years older than the rest of their bodies’ biological ages because of methylation.
Steve and Morgan also created a way to use artificial intelligence to measure our “clock,” which estimates how many years people will live on average. My problem with this is that the measurement is based on the changes in methylation—and methylation may not be such a reversible process. If we give someone a drug that slows aging, the methylation that already exists may not go away. So while this test opens some interesting inquiries, I believe we will eventually come up with better biomarkers to guide us with treatment options. (More about the clock in chapter 9.)
Hands down, the most important intervention we have for aging is physical exercise, which has positive benefits for males and females at every stage of life. Not only does physical activity improve our cardiovascular health, help to regulate our weight, and lower our risk of type 2 diabetes, it may also help to prevent strokes, dementia, and even cancer. Based on the existing evidence, it appears that we’re meant to be physically active throughout our lives, but at some point between ages sixty and eighty, we start to lose energy and muscle strength as the biology of aging affects our whole bodies. Cardiovascular ability also declines with age, so strength training and cardiovascular exercises are particularly important as we get older. The key is to try a wide variety of activities and exercises that increase strength and bolster your cardiovascular system and to stick with the ones you like most. There’s a lot of truth to the adage “Use it or lose it,” and it has to do with more than just staying in shape. It turns out that aerobic exercise also provides some amazing cognitive benefits. (More about that below.)
As we age, it’s also important to retain flexibility by stretching and doing practices like yoga and tai chi that help to maintain balance. My sister Osnat, who is a super trainer with studios around the world, convinced me that flexibility is important throughout life, but even more so as we age. I took her advice and believe it prevented me from having a disability. Flexibility and a good sense of balance can also help to prevent injuries. I stretch for fifteen minutes at least once a week and more often when I can. It’s never too late to start exercising, but it’s imperative that you start slowly if exercise is not already part of your lifestyle. Start by getting clearance from your doctor for the specific exercises you plan to do, and begin by working out at 60 percent of your capacity and slowly building up from there.
As for how much you should exercise, the answer is that we don’t know yet. Just as with caloric restriction, where restricting some calories extends our life span but restricting all calories would kill us, we need to strive to find the optimal ranges for what we’re trying to achieve. The type and amount of exercise that’s best for you may be harmful for someone else; we’re all different. We usually recommend that elderly people exercise for at least twenty-five minutes from three to five times a week. There’s nothing that supports this absolutely, and there’s nothing that disputes it—it’s just a reasonable recommendation for the elderly population in general. When it comes to individuals, we might ask some of them to exercise more often or for longer periods of time.
While the specifics are far from clear, we know that physical activity is crucial to health span and will increase your chances of passing age eighty. The benefits of exercise for both the young and the old are greater than the benefits we have seen from any particular diet.
A study that followed more than 650,000 people over about ten years reported that moderate exercise such as brisk walking for seventy-five minutes a week added almost two years to people’s life expectancy. People who averaged two and a half to five hours of exercise a week gained three and a half years in life expectancy, and people who exercised an hour a day added four and a half years. That said, keep in mind that this is an observational or association study. Maybe the participants who exercised were aging slowly and that’s why they were able to exercise. Maybe healthy diets or a supplement regimen are the reasons for some people’s longevity. Thus, while my belief in exercise is strong, as a scientist, I can’t tell you that the longevity differences reported in this study were absolutely a result of exercise. But I can tell you that I exercise every day. And on days when I’m visiting my sister Netta, I exercise more because I can’t resist her delicious cooking.
There was also a study funded by NIH that concluded that mortality rates for older women (average age seventy-two) who walked about 4,400 steps a day were significantly lower than the rates for those who walked about 2,700 steps a day. Mortality rates dropped even further for the women who averaged more than 4,400 steps a day and leveled off at around 7,500 steps a day. There’s a commonly held belief that 10,000 steps a day is the magic number for staying healthy, but I have to tell you there isn’t much scientific evidence to back that up. And if it does turn out to be the right number for people who are young or middle-aged, that doesn’t mean it might not be too much for some older people.
By the way, how many steps it takes you to walk a mile depends on the length of your stride, and that length tends to decrease with age. But for the sake of calculating, if your stride is a little longer than two feet, it will take a little more than two thousand steps to walk one mile. If you’re active with everyday activities on a regular basis, it’s possible that adding just one mile to your day could be enough to extend your life span and health span.
The interesting thing about exercise is that, in theory, it should be bad for us. It induces oxidative stress, which appears to contribute to aging and disease, and it increases the breakdown of muscle tissue as well as causing some inflammation. And yet exercising is good for us at every age. So what’s going on?
Regular exercise appears to have a positive effect on all the hallmarks of aging, and that may be due in part to a process called hormesis, by which a certain amount of stress can be helpful and protective because it activates many of our natural defenses. Since moderate exercise increases our metabolic rate, it leads to more oxygen free radicals in our cells. We used to think that these free radicals were strictly harmful. But we’ve learned that they have complex effects, some of which are helpful. For example, free radicals notify cells when they’re in danger of being seriously damaged so the cells can turn up their internal antioxidant defenses.
So hormesis, the body’s process of upregulating mechanisms that protect it against oxidative stress, can be thought of as a resilience builder—you build resilience to something toxic by exposing yourself to it. Exposing yourself to the short bursts of oxidative stress that come with exercise builds your defenses against stress in general, and that slows the aging process. Exercise stimulates an enzyme called AMP kinase that helps maintain cellular-energy homeostasis and control lipid metabolism. Exercise also activates the nutrient-sensing protein mTOR, which works against longevity, but the benefits of exercise still by far outweigh the drawbacks.
In addition to hormesis, regular exercise stimulates the machinery in our cells that recycles proteins. This directly targets impaired proteostasis, the hallmark of aging characterized by the accumulation of damaged proteins. Undamaged proteins repair our DNA, which is very important because our DNA is being damaged all the time, and if it’s not repaired, it can cause cancer. Exercise is very good at stimulating autophagy, the process that disassembles damaged proteins and uses the individual elements to make healthy proteins.
THRIVING IN THE SHADOW OF STRESS
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My uncle Ervin Adam seems to be living proof that what doesn’t kill us can make us stronger. In his case, strong enough to not just survive tragedies and natural disasters but to lose everything and start over four times and yet be thriving at ninety-seven years and counting. A Czech native, he spent fourteen months in six concentration camps during the Holocaust, and today, he’s a self-described “youngster” who still attends lectures two or three times a week at Baylor College of Medicine, where he taught for forty-seven years until retiring at age ninety-four. “I have to keep up,” he says in his thick Czech accent, shrugging.
He isn’t reluctant to talk about his time in the camps, but he doesn’t dwell on the hardship he endured. In fact, when he talks about it, there’s the hint of a devilish grin on his face. “When people ask me what I did during World War II, I tell them I made a sightseeing tour of Germany at government expense.”
When you ask him why he was moved around to six camps, he shrugs again. “Because I am a nice fellow. They wanted to show to me more of Germany.”
Actually, his reasons for not re-creating his experience are practical. “You couldn’t understand. You have no idea. What happened there was unbelievable. It took me twenty-four hours to realize where I was. I didn’t know anything about a camp. We never heard about it. But there I was in the middle of it. Fifty years later, how can I explain it so that my grandchildren will believe it? If I was unable to understand it immediately, how can you understand it?”
Even in his autobiography, Everything Is Otherwise (Prague, Czechoslovakia Academia, 2018), he devotes only twenty-five pages to his time in the camps and the genocide that he and his sister, Edith, escaped but that claimed his parents’ lives. Because he survived and eventually found a peaceful life with his family in the United States, he says, “Auschwitz can be forgotten.”
After he was liberated in 1945, he went back to Czechoslovakia and began his medical studies in Prague, with most of his focus on epidemiology and at least a little of his focus on Vlasta Pánková—soon to be his wife. They both became assistant professors of infectious diseases at Prague’s Charles University, but by 1960, they had been kicked off the faculty because they were not Communists. Membership in the Communist Party was a faculty requirement, so Ervin and Vlasta were officially dismissed for providing “insufficient medical-political education” for the university’s students.
They had developed expertise regarding polio, though, which led Ervin to a position at Prague’s Institute of Immunology and Vlasta to a position at a school for the continuing education of physicians. After the Salk polio vaccine became approved for use in Czechoslovakia in 1958, Uncle Ervin played a critical role in its widespread distribution. The government did not receive enough to vaccinate everyone, so they decided to give it to two-year-old children and hope that they would receive more for the rest of the population. To make the supply go further, Ervin suggested that instead of the standard practice of injecting it into the muscle, one-fifth doses could be injected intradermally (into the second layer of skin) for a sufficient immune response. In 1959, the Czech health service agreed to study the safety and efficacy of this trial with the U.S.-made live polio vaccine, and Ervin was a member of the commission in charge of planning and evaluating the trial. As it turned out, it was so safe and effective that in 1961, Czechoslovakia became the first country to eradicate polio, and for his role, Uncle Ervin received the Award Česká Hlava—the Czech equivalent of a Nobel Prize—in 2012. He and Vlasta also received Gold Medals from Charles University in 1989 for lifetime achievements, and in 2004, Uncle Ervin was elected a foreign member of the Learned Society of the Czech Republic (formerly known as Royal Scientific Society).
And then there was his “second life.” In 1968, as the Soviet Army was invading to suppress the liberal reforms of the Prague Spring, he and Vlasta fled with their daughters to Canada, where they stayed a short time before fleeing from violence again. He’d accepted a position at McGill University at a time when Québec separatists were perpetrating bombings in the Montreal area, and when the university became the target of a violent demonstration, he secured a visa and moved the family to Houston, where he joined the faculty at Baylor College of Medicine.
“I’m essentially an adventurer,” he says. “It worked out for us, but I would not advise people to do it. If you have a reasonable life standard, if you are not in danger that you are going to lose it, and if you are not a dreamer, sit on your behind where you are. Don’t move. It’s not easy.”
After so many years of adventure, you might think he would have been ready to retire long ago—if not by age sixty-five, at least by seventy-five. But even at eighty-five, “I didn’t have the guts to retire,” as he puts it. “What would I do in retirement?”
Now that he finally has given up the working life, what does he do to take advantage of the “extra years” he’s enjoying?
Like he said, he keeps up. And not just with medicine. He spends two to three hours a day switching back and forth between right-leaning Fox News and left-leaning CNN because “I want to know what is going on in the United States.” He also reads Czech weeklies that provide intelligent coverage of European news and, often, better coverage of U.S. news than he finds in American publications. “They have much better and more authentic comments.”
Uncle Ervin is a remarkable example of resilience. Like many SuperAgers, he has suffered the stress of hardship and upheaval and hasn’t necessarily abstained from unhealthy habits (he smoked a pipe for twenty-five years). But as surprising as it might seem that Holocaust survivors can thrive for decade after decade and achieve exceptional longevity despite the stress they’ve endured, in some cases it may be the stress that’s responsible, thanks to hormesis. In Uncle Ervin’s case, his time in the camps and the flight situations that have been a theme of his life may have upregulated his defense mechanisms to the degree that they’ve protected him throughout his life.
Hormesis, genes, willpower, or all three? There’s also the possibility that a methylation pattern he developed during the Holocaust has protected him ever since. Whatever the answer is, Uncle Ervin is a powerful inspiration for the Einstein team as we uncover the secrets of aging later.
Exercise is an important component of health throughout our lives but becomes even more important as we age because we become more susceptible to losing muscle and function. Muscle strength, physical performance, and walking speed are commonly used to measure function. Severe muscle loss, called sarcopenia, is one of the age-related changes we sometimes see in very old adults because muscle mass is relatively maintained into our forties and then progressively decline. When we look at the biology of aging, we see that the loss of muscle mass occurs because, as we get older, we stop generating enough new muscle cells to compensate for those we have lost. While muscle mass loss is a concern, losing strength is a more significant problem. A decrease in strength can be related to the quality of muscle itself, or it can be caused by vascular and neural changes that occur when an older nervous system doesn’t tell the muscles to activate or when oxygen and nutrients are impaired. But this isn’t a simple matter to assess, because as people age, they often exercise less and are not as physically active in general, and we know that sedentary behavior can contribute to loss of strength and muscle mass with advancing age.
If left unchecked, muscle loss can lead to poor physical performance, including difficulty with climbing stairs, walking, and rising from a chair, all of which lead to increased risk of falling, disability, and a potential need for long-term medical care. Loss of muscle is also bad for our metabolic health. We start losing muscle mass at about the same age that we see an increase in type 2 diabetes. Muscle is our most important organ for maintaining our sensitivity to insulin, because muscle stores most of the body’s sugar as glycogen, and insulin resistance is a primary element of type 2 diabetes. In addition, people usually don’t change their eating habits as they age, and when they become less active, they tend to accumulate fat instead of burning those calories.
One of the fascinating things we’ve learned about metformin is that it both activates AMP kinase, which is good for longevity, and inhibits mTOR, which is bad for longevity. To gain greater understanding of what appeared to be a win-win interaction, my friend and collaborator Charlotte Peterson, a gerontologist at the University of Kentucky, conducted an NIH-funded study in which two groups of elderly people did the same amount of strength training for fourteen weeks. During that time, one group took metformin and the other group took a placebo. Charlotte’s hypothesis was that since exercise and metformin both activate AMP kinase, together they could be synergistic and amplify the effect. To her surprise, while both groups increased their strength and muscle quality in a clinically significant way, the metformin seemed to inhibit some of the benefits of exercise, in particular the addition of muscle mass. Like in our MILES trial, we studied the transcripts—the message that RNA expressed in muscle biopsies obtained before and after exercise in both groups—and we noticed that exercise without metformin and exercise with metformin had some similar effects on strength. How can it be that they have less muscle but equal strength? How can it be that, per unit of muscle weight, those who exercised and took metformin performed better than those who only exercised? Ameya Kulkarni, my brilliant former graduate student, noticed that one difference was that members of the metformin group had less oxidative damage and less inflammation—some of the bad effects of exercise. Also, metformin inhibits mTOR while exercise increases mTOR; the decrease in mTOR may have caused the muscle to function better. At the end of the day, because the subjects did not have different muscle function, the contradictory advantages of exercise and metformin canceled each other out. Although it looked like metformin did not allow all the positive effects of exercise to occur, there’s a lot of suggestion that the combination of exercise and metformin has a positive overall effect. In light of this, I take metformin in addition to exercising.
One in four older Americans is not getting adequate nutrition, and one in three people aged sixty-five and older has diet-related deficiencies. Malnutrition can contribute to decreased strength, weakened immune response, weight loss, anemia, fatigue, mental fog, and confusion. It can also depress thyroid function and increase the risk of harmful drug interactions. So it should be no surprise that older adults who are malnourished see doctors more often and make more trips to the emergency room. They are also hospitalized more often than their peers who are well nourished, and their hospital stays are almost twice as long and cost $2,000–$10,000 more.
Since you’re interested in healthy longevity, you probably already know about the ketogenic diet, the Mediterranean diet, and what people who live in blue zones eat. But what may be equally important or even more important for long, healthy lives is what these people do not eat. There’s more to good nutrition than following the latest trend, and as with exercise and fasting, dietary recommendations can vary widely depending on individual needs, circumstances, and biological age. But in general, there are five guiding principles to keep in mind:
Calories matter, so paying attention to how much you eat and choosing to eat just a little less at each meal can make a big difference. We’ve known for decades that eating less is healthier than eating more.
In a study published by The Journal of the American Medical Association that compared decreasing food intake with fasting every other day, the participants in each group lost the same amount of weight on average, but those who fasted said they found it easier than they had found restricting calories on previous diets.
1 gram of carbohydrate is about three calories
1 gram of protein is about four calories
1 gram of fat is about nine calories
A gram of fat is the hardest to get rid of, mainly because it has the most calories.
Our bodies use macronutrients, which are the nutrients we get from proteins, fats, carbohydrates, and water, primarily to generate energy and for tissue growth and repair. There’s a lot of discussion about the best ratio of proteins, fats, and carbs, but since aging changes biology, that balance is different at different stages of life. For example, we need protein when we’re younger, but since it activates mTOR, we’ve learned that increasing protein for people after a certain biological age is not the right thing to do. But increasing carbohydrates and fat in the aging population isn’t ideal either, so there’s always some sort of trade-off. The other challenge is that between the ages of sixty and eighty, people in developed countries tend to go from getting too much nutrition to not getting enough. So I don’t know that anyone can definitively declare that a particular ratio of macronutrients is optimal at all stages of life.
A questionnaire-based study published in The Lancet in 2018 looked at how the ratio of proteins, fats, and carbohydrates affected mortality in 15,428 adults from ages forty-five to sixty-four. The lowest risk of death was for people whose diets were 50–55 percent carbohydrates. For people whose diets were 80 percent carbohydrates, the risk increased by up to 10 percent. And for the people for whom carbs made up 20 percent of their diet, the risk increased by up to 60 percent. So a moderate amount of carbohydrates appears to be better for longevity than a diet that’s either high or low in carbs.
But one of the problems with this study is the same problem we have with all diet studies, and that is that people aren’t very good at accurately recording what they eat. So whether or not the people with the best results were actually eating 50 percent carbs, we really don’t know. Even if they were, we don’t know if the results can be attributed to other habits that we are unaware of or cannot measure. As in many studies, the results were statistically adjusted for sex, age, race, total calorie consumption, physical activity, cigarette smoking, diabetes, education, and income level, which all influence mortality. But what if the people with the highest carbohydrate intake were snacking all day long and didn’t have enough of a fasting period to regulate the defense against aging? Whatever the case, though, it’s safe to assume that a diet that’s 65 percent carbohydrates or more is not beneficial.
There is also evidence that people who eat more grain have less mortality than people who eat less grain. But when we take a closer look, we see that they not only were eating more grain but were also eating less beef and might have been getting more exercise than their peers. So the beneficial effects they are experiencing could be from the grains, the exercise, the lower amount of meat, some combination of these factors, or factors we are not even aware of.
Studies also indicate that a diet high in fiber is more important for longevity than a diet low in carbohydrates. High amounts of fiber lower cholesterol, modulate sugar levels, and increase bowel health by keeping things moving through the intestines.
As for protein, studies show that of all the options, meat is the most detrimental to health. In a Loma Linda Adventist Health Study that followed ninety thousand people, those who ate the most meat had about twice as much cardiovascular mortality, while those who ate the most nuts and seeds as their protein sources had 50 percent less mortality. And those who ate less meat and more vegetables had lower body mass indexes, lower incidence of type 2 diabetes, less hypertension, less incidence of cancer, and lower overall mortality.
Processed red meat increased the risk of mortality more than any other protein, but the risk from eating poultry and fish was not significant, and neither was the risk from eating protein from dairy. Eggs appear to increase the mortality rate, though, and there are associations between eating eggs and incidence of cardiovascular mortality. The maximum daily amount of cholesterol recommended in current U.S. guidelines is 200 mg—about the amount contained in one egg. If you increase that to 1,000 mg, you increase your chance of cardiovascular mortality by more than 70 percent, according to a 2019 study reported in The Journal of the American Medical Association. Based on the study’s results, if you eat two and half eggs a day, you increase your risk of cardiovascular mortality by 40 percent. But maybe the markers we see are actually associated with eating breakfast. Since we typically eat eggs for breakfast, if you skip breakfast, you probably aren’t going to have eggs. What would happen if we skipped breakfast and had eggs for dinner? We really don’t know, but skipping breakfast keeps looking better.
When we look at nonvegetarians, semi-vegetarians, pesca-vegetarians, lacto-ovo-vegetarians, and vegans, the BMI goes down progressively from 28.8 for nonvegetarians, which is almost obese, to 23.6 for vegans, which is lean. And the incidence of type 2 diabetes goes down from 8 percent in nonvegetarians to 3 percent in vegans. Yet only about 2 percent of our centenarians are vegetarians, again suggesting that genetic factors are important for health span and longevity and that if we identify those, we can protect against the negative effects of our lifestyles and environments.
While it’s true that water is a macronutrient in the sense that all our organs need it to function, it’s also true that we can drink too much of it. Bottled water is more expensive than gasoline, and we don’t even know how pure that water is in some cases. We do know that the disposable plastic bottles are adding to our plastic problem worldwide, but beyond bottled water being bad for the planet, we just don’t need as much water as the companies selling it want us to believe. In general, men need about four cups of water a day, and women need about three cups. Of course, how much water we need depends on a number of factors, including whether we’re exercising and whether we’re living in or visiting places that are very dry, have high temperatures, or are located at higher elevations. When we drink excessive amounts of water, we lose sodium. There was a case of water toxicity in a young man because the sodium concentration in his plasma dropped so low that he became unconscious and died. This only happens if your kidneys are not healthy, but how do you know if they are?
It is important for the elderly to avoid dehydration, though, and they’re a little more prone to it because their biological sensing of thirst declines with age.
Obesity contributes to type 2 diabetes and other conditions that can shorten our lives, but while we want to avoid becoming fat, we don’t want to stop eating fat because consuming a little of it is good for us and necessary. If you’re as pleased as I am to see the words good and fat together, you’re really going to like the news on the ideal body mass index (BMI). While the stereotypical healthy body is lean, studies that have looked at millions of people, at all ages, around the world have determined that the lowest mortality rates are associated with people who probably have some extra subcutaneous fat, and this applies to men and women of all ages. These studies look at BMI and study what BMI levels are most prevalent for mortality. A measurement of 20–24 is considered healthy, below 20 is underweight, above 25 is overweight and 30 or more is obese. Based on these numbers, we might guess that people who have a BMI in the healthy range would have the lowest mortality. But it’s actually the overweight people with BMIs around 27. Not too fat—just a little fluffy like me. People with BMIs in this range might also have a little more visceral fat, but our subcutaneous fat is protecting us, and that’s probably happening in conjunction with our genetics. Also, high BMI is a strong marker for diabetes, but we don’t know if lower BMIs protect against diabetes or if it’s the diet that’s offering protection.
WHAT’S YOUR BMI?
You can calculate your BMI at https://www.aarp.org/health/healthy-living/info-2017/bmi_calculator.html
As our weight increases, so does our risk for the following conditions:
Losing weight by following a healthy diet can:
While there are important benefits to losing weight, carrying a few extra pounds after we’re age sixty-five may reduce our risk of disability and increase our longevity.
We have more microbial cells—about thirty-nine trillion total—than other cells. These bacteria cells make up our microbiomes, and just like our fingerprints, microbiomes are unique for each person. When people hear the word microbiome, they tend to think of the good bacteria that live in our guts, but these microbial cells are everywhere in our bodies as well as outside it, on our skin. We have known about these cells for some time, and we have known that the microbiome in the intestine is important for processing vitamins A, D, E, and K, but until recently, we were not aware of the profound effects it can have on all systems of the body or its link to many age-related diseases and depression. Several studies, including the NIH’s Human Microbiome Project, have looked at the relationship between our microbiomes and our health spans and life spans, but we still don’t know how microbes affect the biology of aging. That’s likely to change soon because numerous experiments aimed at curing a variety of illnesses and diseases by altering the gut’s microbiome are under way. So far, we have evidence linking the health of the microbiome with digestion, immune response, inflammation, bone density, and cognition.
Although we have more questions than answers, there is no doubt that the microbiome is an important part of our physiology. And when we do experiments in our laboratory by transplanting microbacteria or administering antibiotics in decreasing doses, we can see that there are significant physiological effects. But my biggest interest is in whether the microbiome plays a major role in aging. From what we have seen, the microbiome does not change significantly in aging adults unless they are in hospitals or institutions or they are getting antibiotics, but that doesn’t mean that there aren’t individual differences between balanced and imbalanced microbiomes.
TRILLIONS OF “MOUTHS” TO FEED
The microbiome in the gut seems to benefit from the live bacteria cultures in yogurt and fermented vegetables such as sauerkraut. It appears not to favor antibiotics, laxatives, artificial sweeteners, processed food, or a sedentary lifestyle.
Of all the popular diets that have been in fashion over the years, the only one that was based on a clinical study with interventions and a control group and that has proved to increase health span and life span in humans is the Mediterranean diet. In PREDIMED, a long-term study conducted in Spain, 7,500 men and women who were slightly overweight and at risk for diabetes and heart disease were randomly divided into two groups and studied for five years. One group ate the low-fat diet that was being recommended in the West when the study began, and the other group ate a high-fat Mediterranean diet that was supplemented with either almonds or olive oil. Although many doctors said that olive oil was extremely unhealthy because it was high in calories and a mix of saturated and unsaturated fats, the people in the study who consumed the olive oil had the best results, just slightly better than those who supplemented their diet with almonds. Compared with the group that ate the low-fat diet, those who ate the Mediterranean diet had a third less diabetes, heart disease, and stroke, and they had less cognitive decline. As a bonus, they also lost some weight.
Keep in mind that results like these are rarely attributed to a single factor or a single food. The Mediterranean diet includes a wide variety of vegetables and fruits, whole grains and legumes, small amounts of fish and poultry, and very little red meat. But the olive oil did appear to be the most significant element in the study results. People in Spain, Greece, and Italy, on average, consume more than three gallons of extra-virgin olive oil a year, compared with people in the United States, who average about a quart a year. So people in the Mediterranean are getting twelve times more of this liquid gold than Americans.
ALL OLIVE OIL IS NOT ALIKE
Olive oil’s antioxidant polyphenols have a direct effect on blood vessels and genes, and they feed the good gut bacteria and produce fatty acids that lower inflammation.
In the PREDIMED study, only the extra-virgin olive oil delivered health benefits. Olive oils that were not extra-virgin did not appear to produce any benefits. Cold-pressed extra-virgin olive oil contains about thirty types of polyphenols that reduce inflammation and target the hallmarks of aging, particularly in the cardiovascular system and the brain. It also has lower acidity and tastes better than less healthy olive oils.
If you are concerned that olive oil might produce carcinogens when you cook with it, no negative health consequences were observed among the people in the study who regularly cooked with it.
We’re already seeing some healthier snack options on supermarket shelves, and we’ll see more of them in the coming years. Nutraceuticals and truly healthy snacks are some of the newest products in the works at food production companies. When Pepsi asked the members of its scientific advisory board on which I served to help figure out the types of healthy snacks that would meet the needs of the elderly, we were advised to think outside of the box.
“Well,” I said, “my first recommendation is that you buy Guinness beer. It has lots of nutrients, and besides that, if you give it to the elderly, they’ll be happy, too.”
We laughed, knowing that was never going to happen, but it was a good way to begin the explanation of how nutritional needs change as we age. In general, between the ages of sixty and eighty, people go from being overweight or obese to being thin and malnourished (although their abdominal fat seems to stay the same). This happens at different rates for different people, so the recommendations for best snacks change with aging. Many people who are eighty and older and losing weight can benefit from some high-calorie snacks.
Older people are also losing muscle and proteins, but giving them protein can activate the anti-longevity protein mTOR. (Incidentally, the drug rapamycin blocks mTOR and extends life span.) So high-protein snacks that can be good for younger people may not be a good choice for older people, and neither are snacks that are high in sugar or salt. As a result, elderly people’s options for healthy packaged snacks are a little limited, but discussion is continuing.
We need micronutrients because they play subtle but vital biochemical and physiological roles in cellular processes, including nerve conduction and vascular functions. As we age, our bodies aren’t as efficient at absorbing and using vitamins and minerals, so our need for micronutrients increases. Many older adults are taking medication, and some medications can also interfere with the absorption of nutrients. These factors combined mean that having a nutrition-rich diet becomes even more important as we age. While younger, healthy people can get their nutrient requirements entirely from food and rarely need supplements, this is often not the case for older people, especially if they’re sick. But some vitamins taken in excess or in combination with certain drugs can be harmful. Combining exercise with large amounts of vitamins, such as vitamin E, has even been fatal.
There are some vitamins that, when taken correctly, do not do harm, and for people who have true deficiencies, they may be helpful. For example, when elderly people are losing weight and starting to decline, supplementing their diets with complex vitamins and minerals is considered a safe and beneficial practice. But many people who are age fifty or older may also need to boost their intake of vitamin B12, calcium, and vitamin D.
Check with your doctor to find out if you need more:
We need vitamin B12 to keep our nerve cells and red blood cells healthy.
Rich sources: liver and kidneys, especially from lamb, clams, sardines, beef, trout, salmon, and eggs. But older people may not absorb enough of it from food. B12 is also deficient in some patients who have been taking metformin for a long time. I have lower B12 levels and take monthly B12 shots.
As people age, bones start to lose calcium at an increased rate, and since calcium is a critical ingredient for bone strength and resistance to fractures, it’s very important to get enough.
Rich sources: green leafy vegetables like broccoli, collard greens, kale, and spinach, low-fat dairy products, and nondairy “milk” that’s fortified with calcium. But as with vitamin B12, older adults may not absorb enough of this micronutrient from food.
Vitamin D helps calcium to work, and low levels of vitamin D are associated with a high risk of diseases, so the best thing we can do is expose our skin to more sunlight. Older people aren’t always able to get enough vitamin D in this way, so many are deficient in it. And while vitamin D supplements have shown results with the prevention of fractures in women with osteoporosis, we have not seen dramatic results from supplementation in other studies. Some supplements like vitamin D won’t hurt us, but too much of some vitamins including vitamin E can be harmful, so supplementation should be done under the direction of your doctor.
Rich sources: Sunlight on skin is the only source that we know works. Vitamin D–fortified low-fat milks may help.
When I treat people who are struggling to lose weight, they often say things like, “There should be a pill I can take that lets me eat as much as I want without getting fat.” Not too long ago, this idea appeared to be a pipe dream, but not anymore. The race to develop pharmaceuticals and nutraceuticals that mimic the benefits of caloric restriction is already under way. Some drugs will cause weight loss, while others will mimic the advantages of caloric restriction without causing weight loss and will be appropriate for people who are not obese.
With this in mind, researchers are studying the tiny compounds of molecules called metabolites that circulate in our blood. These compounds are made of amino acids, sugars, and fats, and we’re studying the roles they play in longevity. There are thousands of metabolites of interest, and my colleague Derek Huffman looked at four hundred metabolites that can be measured in plasma. We were looking for metabolites with levels that decrease with age, and we wanted to see if those levels would return to more normal “youthful” levels when we restricted the mice’s calories.
With my funding, Derek began the study with four groups of rats, two of which—one made up of young rats and the other made up of old rats—could eat as much as they wanted. Groups three and four were young rats with restricted diets and old rats with restricted diets. In collaboration with Daniel Promislow, a computation biologist at University of Washington, we identified a metabolite called sarcosine that appeared to be a longevity superhero. In rats, sarcosine levels declined with age, but when we restricted their diets, they went up in both the young and the old. This is exactly the response we were looking for as we went through each of those hundreds of metabolites. Then we decided to measure sarcosine in humans. First, we collaborated with geriatrician Luigi Fontana, then at Washington University, who follows the CRONies, and we compared the metabolites of young and old CRONies with those of a control group of young and old people. We got exactly the same results as we got in rats; in the control group, sarcosine was high in young people and went down with age. Sarcosine declined slightly with age in the CRONies, but it remained higher than the sarcosine levels in the control group.
Next, we needed to find the cellular mechanism that’s implicated by which sarcosine targets aging. At Einstein, when Ana Maria Cuervo, codirector of our institute, administered sarcosine to animals and examined what happened with the cells’ ability to carry out autophagy, which becomes less efficient with age, the sarcosine significantly enhanced one of the processes of autophagy in the same way that caloric restriction in animals enhances this process. Ana Maria is a member of the American Academy of Arts and Sciences and the National Academy of Sciences and one of the best scientists and colleagues I could hope for, and together we proceeded to our next experiment.
The next question was how to capitalize on our discovery that sarcosine is something that declines with age but remains higher with caloric restriction. Sarcosine is found in such natural sources as turkey, ham, egg yolks, vegetables, and legumes, but it may be difficult to get enough of it through our diets alone. Since sarcosine is a nutraceutical, however, it could be available immediately, and the results could be astounding. Derek is also looking at drugs that will target the sarcosine pathway and cause an increase in its levels.
In recent years, we have learned that health and longevity are affected not only by what we eat and don’t eat but also by when we eat and how long we fast between meals.
There’s a lot of ongoing research about fasting, and what we’re learning is so promising that I’m experimenting with fasting myself. There are different schools of thought on how we should fast and for how long; at the moment, it’s commonly thought that the best results occur when the fast is done for sixteen to twenty-four hours at least once or twice a week, but this recommendation isn’t based on much data from humans. To enhance our understanding of the effects of intermittent fasting, Rajat Singh, a molecular pharmacologist at Einstein, is trying to determine the minimum amount of time we need to fast to enhance the biological processes that protect us against aging hallmarks such as impaired autophagy. I’m fasting for sixteen hours a day because that’s how long it appears to take for our bodies to use up stored sugar called glycogen. Then insulin levels drop to adapt to the presence of less sugar and enhance the liver’s ability to provide as much glucose as needed. When there is less insulin, there is less mTOR and more autophagy. While insulin levels are low, the body taps into its fat storage, and fat is released into the bloodstream. When those fats reach the liver, they are turned into energy molecules called ketones, which appear to sustain us through the stress. And while there isn’t much scientific data on how a ketone-rich diet affects humans, it has been shown to extend life span in animals. We are also looking at how ketones affect cardiovascular health, blood pressure, LDL cholesterol, triglycerides, and insulin sensitivity, so ketones may play a big role as we study the benefits of fasting for humans.
Although it’s not practical for everyone, based on what we learned from our caloric restriction experiments at Einstein, fasting daily may generally produce the best results. Initially, we thought that restricting calories was responsible for the positive results we were seeing—the animals’ health span was improved, and their mid and maximal life span increased significantly. But since we had been feeding them only once a day, we realized that the results were more about fasting than restricting calories! And in recent studies, the calorically restricted rats that were fed a limited number of calories throughout the day were lean like the calorically restricted rats that ate all their food in the morning. But the rats that ate throughout the day did not live as long, and the rats that ate once a day also demonstrated better cognition and retained their physical functions for much longer than the other rats. So based on such studies, it looks like how often we eat and how long we fast are more important than restricting calories. And for many people, including myself, it’s also easier to do than counting calories.
Thanks to research that AFAR has supported, new findings about the advantages of fasting in animal studies have led to a variety of fasting programs that are being tested with people to see if the effects are as profound as they are in animals. Biogerontologist Valter Longo suggests doing a five-day fasting-mimicking diet three or four times a year. In his book The Longevity Diet, Valter explains that the foods we eat affect us at a cellular level. Our cells all have nutrient sensors that can switch hundreds of genes on or off, depending on what we eat. Some nutrients are more triggering for those sensors than others are, so Valter created diets with foods that avoid triggering them. In this way, the diet mimics fasting, and with mice, these diets have been successful in reversing diabetes. Another lifestyle guru, my friend Peter Attia, M.D., does zero fasting, a seven-day fast with almost no calories, four times a year.
Other fasting-related research is focused on the times that we eat and how they are in line with our bodies’ natural rhythms—or not. Circadian rhythms are the day-to-night, light-to-dark cycles that affect all people and animals. Satchin Panda, an expert on circadian rhythm research at the Salk Institute, has found that aligning our eating with these rhythms is one pathway to good health. In The Circadian Code, he explains that having our meals between early morning and early evening is healthier than eating all day long and then snacking at night. Essentially, you would fast for fourteen to sixteen hours under this plan, so it shares a number of commonalities with intermittent fasting. With mice, restricting calorie intake to eight to ten hours a day has improved their health even when they were eating a diet high in fat and sugar. In humans, short-term studies have shown that intermittent fasting is an effective way to control weight, and it seems to have many benefits beyond weight loss.
All these programs have merit, but fasting for at least sixteen hours is showing the most promise for life span and health span, which is why I’m doing it. I have also lost some weight, but that’s just a nice side effect, not the reason I started this practice. When I share my personal example with people, it surprises me that so many of them think I’m harming myself by skipping breakfast. “Breakfast is the most important meal of the day!” they assure me. But guess what—there is no scientific evidence to support that, and in fact, if you’re trying to lose weight, skipping breakfast might be a good idea. Several valid studies have concluded that eating breakfast can lead to weight gain. When you think about it, it’s not likely that breakfast was part of the plan for our prehistoric ancestors, who spent the day hunting, fishing, and gathering grains, seeds, nuts, and small fruits. It’s not as if Wheaties or Special K were available in the morning, and it’s safe to say that nobody was obese. The carb-heavy morning meal did not become popular until modern times. Bottom line: Infants and children may benefit by eating breakfast, but for adults, it’s not biologically necessary, and skipping it as part of intermittent fasting may contribute to a longer, healthier life.
Sleep is often grouped with diet and exercise as one of the three keys to good health, so we expected to see a link between sufficient sleep and longevity, but our research did not show that link. Some of our centenarians report sleeping an average of eight hours a night and napping during the day—a nice amount of sleep—and we thought that might be a factor in their longevity, but it turned out that some of them are napping because they don’t sleep well at night. Lavy Klein, a visiting professor from Israel, analyzed our sleep data and did find something else that was interesting, though—the centenarians in our study appear to have longevity genes that protect them from diseases associated with sleep disorders, so whether they’re sleeping enough or not, they are not getting those diseases.
Among the centenarians’ offspring and the control group, a significant number of people regularly experience sleep disturbances, and many in the control group have diabetes, cardiovascular disease, and other diseases linked to sleep deprivation while the centenarians’ offspring do not. So while longevity genes are not insurance against sleep disturbances themselves, they do appear to protect against their worst effects. For those of us who were not born with the longevity genes, though, it certainly makes sense to sleep as well as we can to head off the diseases that can result from sleep disorders and deprivation.
In 2017, the Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for figuring out how biological clocks work by doing research with fruit flies. Biological clocks keep flies, fish, frogs, plants, and people on schedules that are about twenty-four hours long whether we know if it’s day or night or not. Our biological clocks are run by “clock genes” that make a protein when they’re turned on. Once a particular amount of the protein accumulates, it turns the clock genes off. But the protein degrades with time, and when it drops to a certain level, the clock genes switch back on. The cycle affects nearly all our bodies’ systems.
The scientists were initially surprised to discover that the clock genes don’t just exist in the brain—they found them in many parts of the fly. And now we know that we have these clock genes throughout our bodies. In addition to our brains, our hearts, lungs, livers, and other organs have the genes. They even exist within individual cells, and that’s why cells tend to do repair work and cell division at certain times. These findings have very promising implications. For example, they suggest it might be more effective to take medications or treatments at certain times rather than others.
We are also seeing that animals with the best clock genes may live longer. In one study, the mice that had the most reliable clock genes—the ones that maintained a twenty-four-hour-day cycle even in total darkness—outlived the mice that had clocks that did not maintain such a regular cycle.
We have known for some time that people whose sleep patterns are disrupted by working night shifts are at higher risk for a variety of conditions and diseases than people who work during the day and sleep at night. Over time, night shift workers tend to experience more ulcers, heart disease, diabetes, and cancer. They also experience more insomnia, depression, and dementia. And Ana Maria Cuervo’s research has shown that the clock genes change autophagy, like a garbage disposal, and that activating autophagy activates clock genes. Once we learn more about clock genes and how they work, we will be able to time medical treatments and interventions so they have the most positive benefits. Meanwhile, drug developers are exploring medications that might offer protection against sleep disturbances and irregular schedules.
Another way we can increase our chances for longer health spans and life spans is by taking steps to offset genetic mechanisms with lifestyle choices and—when they become available—new drugs that will be designed to specifically target those mechanisms. What we need to keep in mind is that genetic information is in no way a diagnosis, and many times, it is not even a strong indicator that we may develop particular diseases or conditions later in life. But it can offer some helpful information, and that’s why so many companies are offering genetic testing. For example, 23andMe provides ancestry information and also gives you the option to learn about your DNA with regard to health and longevity. Not everyone wants to know about their genes, and we have to respect that, but for those who do want to know, these types of tests may help us to delay or stop the potential onset of diseases. If a woman has the BRCA1 mutation that’s associated with a very high risk for breast cancer, for instance, and her mother, sisters, and aunts have had cancer, she may decide to eliminate her risk by having her breasts and ovaries removed relatively early in life. And people with the APOE4 genotype, which is a strong predictor of Alzheimer’s, may qualify to participate in studies testing drugs that can prevent cognitive decline.
But while these two genotypes are associated with diseases in many studies, we still have to look at their predictive values. In other words, if you have a particular genotype, what are your chances of getting the associated disease? The answer to that question isn’t clear. While BRCA1 has a very high penetrance—the proportion of people with a gene variant associated with breast cancer—most genotypes have undetermined penetrance. So at least for now, genetic tests are not as good at predicting diseases as lab tests that measure cholesterol, glucose, and blood pressure.
Remember that when we did gene sequencing with forty-four of our first centenarians, they had more than 230 genotypes that were associated with diseases they did not have because they also have other differences that protect them from the hallmarks of aging. We have also seen the CETP genotype associated with both improved cognitive function and cognitive decline, and we’ve seen that CETP’s effects are not universal. So part of the challenge is that it’s never about a single genotype. In fact, looking at genotypes in isolation makes no sense because we’re not built from one variant at a time, but that’s how we analyze the information. We’re built from many, many variants, and some of them can cancel each other out, and some of them can amplify each other. It’s so complex that genetic testing is not always predictive, but it can give us a chance to be proactive. If you do choose to have genetic testing done, be sure the results are being interpreted in ways that put the finding into context, because getting genetic information without a clear explanation or without counseling can be unnecessarily stressful.
In the case of my own genetic testing, I found out that I’m at “risk” for having perfect pitch. My son and daughter, who both play the piano, have tested me and say it seems to be true. It’s possible that if my parents had known that when I was young, they would have encouraged me to pursue a career in music, and I may not be a doctor writing a book today but a conductor.
While that information was mostly just entertaining, I did learn something else that might provide a clue to why I tend to test low for vitamin D. The test said I had a slight risk for lactose intolerance. I don’t suffer when I eat cheese, and I love it, so I still eat it, but it’s possible that eating dairy may speed up my digestive system’s transit time, and that could mean my body doesn’t have enough time to absorb the vitamin D. Whatever the case, I take vitamin D supplements because they might help and won’t hurt.
A concern I hear about DNA testing is that the results might prevent people from getting insurance coverage if the preexisting conditions clause is eliminated or could work against them in some other way. Keep in mind that this information is private, and while it can be predictive, there are way too many variables to conclude that any genetic variant in and of itself is going to result in the associated disease. Even in the case of the BRCA1 gene with its high penetrance, not everyone is going to get cancer. Your cholesterol and glucose levels, blood pressure, and family history for diseases are much more predictive than genotype, and your doctor and insurance company already have that information, so disclosing a genotype is usually not going to put you at additional risk.
PREVENTION MATTERS
The following diagnostic tests and vaccines are recommended:
Diagnostic Tests
We know that biological age and chronological age differ, but to be on the safe side, we should have all these tests by the time we’re fifty.
Blood Glucose/HbA1C
Blood Pressure
Colonoscopy
HDL and LDL Cholesterol and Triglycerides
Mammogram
Pap Smear
Prostate Cancer Check
Vaccines
Flu Shots*
Pneumococcal
Shingles
Td/Tdap
*Although we encourage the elderly to get flu shots, they often don’t, because many of them know that it doesn’t guarantee that they won’t get the flu. Most immunization protects people completely, but the immunization for the flu is about 40 percent effective and possibly only 20 percent effective in the elderly population. But I still recommend flu shots for the elderly, because if they get the flu, many of them will need to be hospitalized, and they dislike that more than most things.
Aerobic exercise and diet may have as much of an effect—and possibly even more of an effect—on keeping our minds clear and sharp as brain workouts do. Everyone knows that exercise is good for the body, but we didn’t know how good it was for the brain. Recent studies suggest that exercise may be even more important than staying mentally engaged when it comes to staving off cognitive decline and dementia. And we’re also learning more about the link between nutrition and cognition.
Epidemiologist and clinical dietitian Claire McEvoy is working toward increasing our understanding of how diet affects cognitive health as we age. She’s looking specifically at the Mediterranean diet and other heart-healthy dietary habits because what’s good for the heart often proves to be good for the brain, too. When she looked at the Mediterranean diet as part of the Health and Retirement Study and the Coronary Artery Risk Development in Young Adults study, she found that both older and younger people who ate this way had better cognitive health. Another study found that eating the Mediterranean diet as young adults can help to keep cognitive function stronger at midlife.
Based on these and other similar studies, what we eat may have cumulative protective effects on our brain function throughout our lives. If so, eating well throughout our lives can help to slow the onset of cognitive decline and may reduce the risk of dementia later in life. High-quality diets such as the Mediterranean diet also have anti-inflammatory and antioxidant effects, and these effects may also help to protect from dementia and Alzheimer’s as we age. But this quest is far from over. We still have a lot to discover and learn before we’ll be able to recommend an optimal combination of nutrients and foods for lifelong brain health.
Researchers are also looking for connections between sleep and brain health. While the connections between mental health and sleep aren’t as clear as those between mental health and exercise and nutrition, we’re starting to gain more understanding in this area. Researchers, including Kristine Yaffe, a neuropsychiatrist from the University of California–San Francisco School of Medicine, has been looking at how disrupted sleep might contribute to dementia. A study published in the journal Sleep found that people whose sleep was often disrupted had a 1.68 times greater risk for cognitive impairment, including Alzheimer’s, than people who slept well. But the researchers were careful to point out that it’s not clear whether sleep disorders cause cognitive decline or are a symptom of it. A study published in Science in 2019 connects more of the dots, though. Researchers David M. Holtzman, M.D., and Brendan P. Lucey, M.D., explored how a lack of sleep is connected to an increase in two proteins associated with Alzheimer’s. One of the proteins, called tau, was also found in excess in adults who were extremely sleep-deprived. Other reports on sleep-deprived adults showed that the protein amyloid-beta (A-beta) was present in their brains in high levels, and this protein is also seen in excess in the brains of people who have Alzheimer’s disease.
In one study, eight adults were monitored during a night of normal sleep and also over the span of thirty-six hours without sleep. Samples of their cerebrospinal fluid showed a 51.5 percent increase in the tau protein (a biomarker for Alzheimer’s disease) in participants who were deprived of sleep. This was similar to the results of a study done with mice in which the sleep-deprived mice had twice as much tau as the mice that slept. Since both tau and A-beta increase when we don’t get enough sleep, researchers are looking at how treating sleep disorders in midlife and finding treatments to help people get enough sleep can decrease the risk for Alzheimer’s. While we sleep, the brain seems to dispose of debris, including excess proteins, so it’s possible that when we don’t get adequate sleep, our disposal systems don’t have enough time to do their jobs.
While the connections between sleep and staying mentally sharp are still being researched, we do know that there is a clear association in older adults between getting good sleep and psychological well-being. But we haven’t seen the same connection between quantity of sleep and psychological well-being. So if you’re sleeping less as you age but still feeling good during the day, sleeping less may be normal for you. But if you’re sleeping poorly and it’s affecting what you can do during the day or making you feel impatient or anxious, you should discuss the changes with your doctor.
The Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study led by George W. Rebok of the Johns Hopkins Center on Aging and Health, suggests that reasoning, memory, and how fast thoughts can be processed can be maintained with cognitive training. In this study with 2,832 participants, those who engaged in mental exercises maintained these abilities for ten years longer than the control group. Our SuperAgers attend lectures, work crossword puzzles, use modern technology, and actively engage with the world around them. Drugs are being tested that will give us all the same genetic edge that they have, but in the meantime, it’s a good idea to keep your brain “in shape.” My colleague Joe Verghese, Einstein’s chief of geriatrics and a partner in some of our grants, has shown that mental engagement such as working crossword puzzles delays cognitive decline. New types of brain exercises and games that can help to preserve memory and the speed that our brains process thoughts are in the works, although so far there’s little evidence that supports some of the claims being made by the producers and manufacturers. But there is sophisticated technology that combines virtual reality with brain imaging that can show where and how various types of training can activate the brain and lead to improved memory.
In other promising research, Adam Gazzaley, M.D., Ph.D., and director of the Neuroscience Imaging Center at the University of California–San Francisco, and his team observed that when adults aged sixty to eighty-five were trained on a game called Neuroracer, they experienced improvements in their abilities to multitask, their working memories, and their abilities to sustain attention that lasted for six months or more. This study shows that some computer games may be more effective than some of the traditional brain-training games done with pencil and paper, but before buying these new products, be sure to investigate the claims to see if quality research backs them up.
At Einstein, we use a variety of tests to measure cognition; Joe designed one that you can do at home called Walking While Talking. In it, he asks elderly people to walk twenty or thirty feet at their regular pace. Then he asks them to talk while they walk and observes whether they slow down. They’re walking slowly to begin with, so when they slow down, it’s not because they’re getting winded or tired—it’s because our ability to multitask declines with age. The next test is to ask them to solve simple math problems as they walk, and those tests become progressively more mentally challenging. In this way, we can find out which tasks are slowing them down the most and what parts of cognition they need the most support with.
Keep in mind that doing poorly on some of these tests does not mean that someone has dementia. It just means they have abilities they need to compensate for or approach differently, and multitasking is usually one of them. But it’s important to keep in mind that while some abilities of older adults decline, other abilities emerge. Dr. Tsvi Lanir in Israel found that older people’s brains become biologically wiser. They can see the end point faster and take shortcuts to get there, so in this way their mental processing is faster than younger people’s. Older people’s brains also have gained the ability to modulate their emotional responses, which is why they tend not to overreact and often become peace seekers.
There is a significant amount of data from scientific studies that suggests that people who have a strong sense of purpose are healthier and enjoy a higher quality of life than people who do not. In one study, researchers wanted to find out if there is a link between having a life purpose and mortality among older people in the United States.
Based on data from 6,985 adults from ages fifty to sixty-one and their spouses of varying ages, the Health and Retirement Study found that people with a strong purpose in life lived longer than people who did not. The researchers also concluded that living purposefully may have health benefits. Since life purpose is a mortality risk factor that people can change, future research will be looking for methods and practices that can help people to identify and strengthen their life purposes. It will also be interesting to see if life purpose affects health through biological mechanisms. As long as you have more plans than achievements, you’ll probably be hanging in here for a while.
Positive attitude was the fourth most common reason the SuperAgers thought they lived longer than their peers, and we were curious to see if the science would support that theory. So we decided to look at whether a positive attitude toward life, together with some other psychological factors like emotional expression, could be a factor in exceptional longevity. For this study, Kaori Kato, a student at the Ferkauf Graduate School of Psychology at the time, developed a brief personality measure to characterize the centenarians. The results showed that the group of centenarians had a positive attitude toward life—they were optimistic, easygoing, outgoing, and laughed often. They expressed emotions instead of bottling them up and had significantly less depression and anxiety than the control group. They also scored higher than the control group in extroversion, agreeability, and conscientiousness. Kato’s findings suggested that the presence of certain personality characteristics may be associated with favorable cognitive and mental health outcomes in advanced age, but the findings do not show whether the centenarians had had a positive attitude throughout life or if it developed later in life. So we don’t know if this great personality that we saw at one hundred had anything to do with their reaching that age.
This became obvious one day after I met with a new centenarian in our study. Max was 104, extroverted, optimistic, and very agreeable, and he had nothing but kind things to say about all his family members. I had fun talking with him and thoroughly enjoyed our time together. Shortly after our visit, I bumped into his son, who is also in our study, and told him his father was one of the nicest guys I’d ever met. The son laughed. “You should have seen the son of a bitch when he was my age,” he said. “He was terrible.”
That’s when I wondered how many of the delightful centenarians had been less pleasant when they were younger. What had happened to the one I’d just met to change him from “terrible” at age eighty to terrific twenty years later? We really don’t know much about the aging brain beyond the age of eighty, but there have been studies that suggest that older people pay more attention to the positive than the negative and remember more of the positive, too. In a study comparing the recollection ability of young people and older people, University of Pennsylvania researchers showed the subjects a wide range of slide images, from very pleasing images like a beach at sunset to disturbing images like a pizza crawling with cockroaches. The young people recalled it all—the good, the bad, and the ugly. But the older people mainly recalled the pleasing slides, which suggests there’s some biology at work when it comes to our enjoyment of the aging process.
There is ongoing research regarding mind-set and health, and in 2019, JAMA published a study that found that being optimistic was associated with a lower risk of cardiovascular events, while being pessimistic was linked to a higher risk of these events. These findings came by way of a meta-analysis of fifteen studies that included 229,391 participants. This information is very promising, because mind-set is something that can potentially be changed and may become a new focus for clinical intervention.
There are many practices that appear to be beneficial and have been safely employed for many years. Practices like yoga, meditation, guided visualization, and reflexology are doing good things for people, and some people swear by the healing powers of listening to certain types of music, singing, or chanting. Others say that creating artwork or expressing themselves through dance keeps them feeling inspired or has helped them to heal. Just because we don’t know how the biology of something works doesn’t mean it’s not beneficial, so practices that can enhance health and happiness without the risk of doing harm are worth exploring.
In just about every interview I do, I’m asked what I do myself to stay young. I’m happy to share that with you, but only with the caveat that what works for me may not be the right things for you.
I started exercising regularly mainly so I could eat more of the great food I love. But later, I learned that exercising does not have as much impact on weight loss as eating less. If you exercise for thirty minutes, you can burn about three hundred calories. But if you reduce your daily food intake by 20 percent, you eliminate about six hundred calories. But exercise helps us to stay younger at any age and no matter what our condition, so I’ve made it part of my everyday life.
Almost every day, I run three miles on my treadmill or I bike ten miles. I also take advantage of the new technology and track my steps with a Fitbit and an iPhone. I think it’s motivating to keep track and even though we don’t know that ten thousand steps a day is the minimum requirement, I’d rather do more than the minimum.
Once a week
Once a week with a trainer
I try not to overdo it with carbs or dessert, but for the most part, I eat anything I want for dinner and put off eating the next day for as long as I can. That may mean having a late lunch or not eating until dinner, but I make sure I stay hydrated with water and noncaloric drinks, including tea and coffee. If I need a snack, I eat several almonds or olives but very few carbohydrates that are poorly absorbed. I often fast on consecutive days, eating only in the evening, and I’ve been surprised by how easy it is and how well I feel.
I have also been monitoring my glucose levels with FreeStyle Libre 14 day system. It’s a tiny patch that holds a needle that’s implanted in the back of my arm and a monitor about half the size of an iPhone. I don’t see or feel the needle, and it doesn’t affect anything I do. When I want to know what my blood sugar is, all I have to do is turn on the monitor and hold it over my arm. I was curious to see what happened with my glucose levels after fasting and exercising and how the levels changed based on what I ate, and some of the readings have surprised me. For example, after fasting for seventeen hours, I ate a tuna salad sandwich on rye bread, and my glucose levels shot up to 170, which is quite high. If I’d had a blood test at that moment, the results would have said I was diabetic. After this experience, I was worried about what my glucose level would be after I ate my favorite meal—chicken paprikash. To my pleasant surprise, the meal barely budged my glucose level after I’d fasted for sixteen hours! So this is just another example of how personal nutrition is and why we need to monitor how we feel after eating or not eating certain foods.
I take NMN, which is a precursor of an energy mediator called NAD+. (NMN stands for nicotinamide mononucleotide and is believed to activate genes that are related to longevity.) We can’t live without the coenzyme NAD+ (nicotinamide adenine dinucleotide), and studies have indicated that NAD+ appears to decline with age. David Sinclair and others have shown the health benefits of mice that were fed NMN or other NAD+ precursors. They could run longer than the mice that didn’t get this supplement, stayed healthier for longer, and died later. As a physician, I didn’t want to do anything that had not been proved in a double-blind study, but when I turned sixty-two, I decided I should include some things in my diet that I believe are safe, even if we don’t have all the answers yet.
The one thing that I noticed with taking NMN is that, according to my Fitbit, my REM sleep has become better.
I’ve been taking aspirin for thirty years even though recent studies have not documented its effectiveness in preventing heart attacks, strokes, or even colon cancer. In fact, a big trial showed that aspirin may be harmful in people who are over the age of seventy, but I take it because I fly frequently and want to protect myself from deep vein thrombosis.
I try to get seven hours of sleep every night, and my Fitbit also gives me information about my sleeping patterns. This is helpful because sometimes I don’t feel like I’ve slept well, but the Fitbit indicates I have. The sensation of not feeling well rested can occur if we wake up while we’re dreaming.
Every day, my life is filled with interesting questions and pursuits, so I’m always thinking.
The internet teems with the latest news on how to stay young, but many of those stories are incomplete or misleading. Although learning how to cut through the noise and decipher what’s real science and what isn’t can seem daunting, doing due diligence and discussing new research with your doctor will help you to determine how the news might be beneficial for you. The information I have shared is limited to practices and treatments that have been rigorously tested, and I have also touched on some possibilities that are promising and should not do harm. But again, choices should always be made on an individual basis.
Make sure there’s scientific research to back up claims, as well as clinical studies done with humans, and find out who funded the research. If a study is supported by organizations like AFAR and NIH that are dedicated to real science, they have merit. But many studies are tilted toward a particular outcome and therefore don’t meet the criteria that reputable journals like JAMA require before publishing them.
You also want to explore any associated side effects. Even some of the safest supplements and herbs can become dangerous in combination with certain pharmaceuticals or procedures. If there is any chance that a treatment or a drug can do harm, be sure to discuss it with your doctor.