Outlive: The Science and Art of Longevity

Metadata

• Title: Outlive: The Science and Art of Longevity
• Author: Peter Attia MD and Bill Gifford
• Book URL: https://amazon.com/dp/B0B1BTJLJN?tag=malvaonlin-20
• Open in Kindle: kindle://book/?action=open&asin=B0B1BTJLJN
• Last Updated on: Saturday, December 9, 2023

Highlights & Notes

There comes a point where we need to stop just pulling people out of the river. We need to go upstream and find out why they’re falling in. —Bishop Desmond Tutu

the odds are overwhelming that you will die as a result of one of the chronic diseases of aging that I call the Four Horsemen: heart disease, cancer, neurodegenerative disease, or type 2 diabetes and related metabolic dysfunction. To achieve longevity—to live longer and live better for longer—we must understand and confront these causes of slow death.

Longevity has two components. The first is how long you live, your chronological lifespan, but the second and equally important part is how well you live—the quality of your years. This is called healthspan, and it is what Tithonus forgot to ask for. Healthspan is typically defined as the period of life when we are free from disability or disease, but I find this too simplistic. I’m as free from “disability and disease” as when I was a twenty-five-year-old medical student, but my twenty-something self could run circles around fifty-year-old me, both physically and mentally. That’s just a fact. Thus the second part of our plan for longevity is to maintain and improve our physical and mental function.

This is always sad to see, and it reinforces one of my core principles, which is that the only way to create a better future for yourself—to set yourself on a better trajectory—is to start thinking about it and taking action now.

But in every case, we are intervening at the wrong point in time, well after the disease has taken hold, and often when it’s already too late—when the eggs are already dropping.

I believe that our goal should be to act as early as possible, to try to prevent people from developing type 2 diabetes and all the other Horsemen. We should be proactive instead of reactive in our approach. Changing that mindset must be our first step in attacking slow death. We want to delay or prevent these conditions so that we can live longer without disease, rather than lingering with disease. That means that the best time to intervene is before the eggs start falling—as I discovered in my own life.

One macronutrient, in particular, demands more of our attention than most people realize: not carbs, not fat, but protein becomes critically important as we age. Exercise is by far the most potent longevity “drug.” No other intervention does nearly as much to prolong our lifespan and preserve our cognitive and physical function. But most people don’t do nearly enough—and exercising the wrong way can do as much harm as good.

Finally, as I learned the hard way, striving for physical health and longevity is meaningless if we ignore our emotional health. Emotional suffering can decimate our health on all fronts, and it must be addressed.

The time to repair the roof is when the sun is shining. —John F. Kennedy

Risk is not something to be avoided at all costs; rather, it’s something we need to understand, analyze, and work with. Every single thing we do, in medicine and in life, is based on some calculation of risk versus reward. Did you eat a salad from Whole Foods for lunch? There’s a small chance there could have been E. coli on the greens. Did you drive to Whole Foods to get it? Also risky. But on balance, that salad is probably good for you (or at least less bad than some other things you could eat).

My point is that a physician who has never done any harm, or at least confronted the risk of harm, has probably never done much of anything to help a patient either. And as in the case of my teenage stabbing victim, sometimes doing nothing is the riskiest choice of all.

You can’t use a tool that has not yet been invented.

This is why I believe we need a new way of thinking about chronic diseases, their treatment, and how to maintain long-term health. The goal of this new medicine—which I call Medicine 3.0—is not to patch people up and get them out the door, removing their tumors and hoping for the best, but rather to prevent the tumors from appearing and spreading in the first place. Or to avoid that first heart attack. Or to divert someone from the path to Alzheimer’s disease. Our treatments, and our prevention and detection strategies, need to change to fit the nature of these diseases, with their long, slow prologues.

First, Medicine 3.0 places a far greater emphasis on prevention than treatment.

Second, Medicine 3.0 considers the patient as a unique individual.

The third philosophical shift has to do with our attitude toward risk. In Medicine 3.0, our starting point is the honest assessment, and acceptance, of risk—including the risk of doing nothing.

The fourth and perhaps largest shift is that where Medicine 2.0 focuses largely on lifespan, and is almost entirely geared toward staving off death, Medicine 3.0 pays far more attention to maintaining healthspan, the quality of life.

We want more out of life than simply the absence of sickness or disability. We want to be thriving, in every way, throughout the latter half of our lives.

Health insurance companies won’t pay a doctor very much to tell a patient to change the way he eats, or to monitor his blood glucose levels in order to help prevent him from developing type 2 diabetes. Yet insurance will pay for this same patient’s (very expensive) insulin after he has been diagnosed. Similarly, there’s no billing code for putting a patient on a comprehensive exercise program designed to maintain her muscle mass and sense of balance while building her resistance to injury. But if she falls and breaks her hip, then her surgery and physical therapy will be covered.

As I tell my patients, I’d like to be the navigator of your ship. My job, as I see it, is to steer you through the icefield. I’m on iceberg duty, 24-7. How many icebergs are out there? Which ones are closest? If we steer away from those, will that bring us into the path of other hazards? Are there bigger, more dangerous icebergs lurking over the horizon, out of sight?

Which brings us to perhaps the most important difference between Medicine 2.0 and Medicine 3.0. In Medicine 2.0, you are a passenger on the ship, being carried along somewhat passively. Medicine 3.0 demands much more from you, the patient: You must be well informed, medically literate to a reasonable degree, clear-eyed about your goals, and cognizant of the true nature of risk. You must be willing to change ingrained habits, accept new challenges, and venture outside of your comfort zone if necessary. You are always participating, never passive. You confront problems, even uncomfortable or scary ones, rather than ignoring them until it’s too late. You have skin in the game, in a very literal sense. And you make important decisions. Because in this scenario, you are no longer a passenger on the ship; you are its captain.

Strategy without tactics is the slowest route to victory. Tactics without strategy is the noise before defeat. —Sun Tzu

I call this the Marginal Decade,

I ask all my patients to sketch out an alternative future for themselves. What do you want to be doing in your later decades? What is your plan for the rest of your life?

This is called squaring the longevity curve.

The point is that the tactics are what you do when you are actually in the ring. The strategy is the harder part, because it requires careful study of one’s opponent, identifying his strengths and weaknesses, and figuring out how to use both to your advantage, well before actually stepping in the ring. In this book, we will apply this three-part approach to longevity: objective → strategy → tactics.

Every moment we are alive, our risk of disease and death is tugging at us, the way gravity pulls a long jumper toward earth.

this is how the centenarians achieve their extraordinarily long lifespans: they delay or prevent the onset of chronic disease, by decades compared to the average.

The second vector of deterioration is the decline and eventual loss of function of our physical body. This may precede or follow cognitive decline; there is no predetermined order. But as we grow older, frailty stalks us. We lose muscle mass and strength, along with bone density, stamina, stability, and balance, until it becomes almost impossible to carry a bag of groceries into the house. Chronic pains prevent us from doing things we once did with ease. At the same time, the inexorable progression of atherosclerotic disease might leave us gasping for breath when we walk to the end of the driveway to fetch the newspaper (if newspapers still exist when we are old). Or we could be living a relatively active and healthy life until we fall or suffer some unexpected injury, as Sophie did, that tips us into a downward spiral from which we never recover.

No matter how ambitious your goals are for your later years, I suggest that you familiarize yourself with something called the “activities of daily living,” a checklist used to assess the health and functionality of elderly people. The list includes such basic tasks as preparing a meal for oneself, walking without assistance, bathing and grooming, using a phone, going to the grocery store, handling personal finances, and so on. Now imagine living your life without the ability to feed or bathe yourself or walk a few blocks to meet friends for coffee. We take these for granted now, but to continue to live actively as we age, retaining even these minimal abilities, requires us to begin building a foundation of fitness and to maintain it diligently.

To live to the age of one hundred without our mind and our body intact is not something that anyone would willingly choose. Similarly, to have the greatest quality of life, only to have it cut short at a young age, is also undesirable. And to retain good health as we age, but without love and friendship and purpose, is a purgatory I would not wish on my worst enemy.

As we will see in later chapters, cognitive, physical, and even emotional deterioration can all be slowed and even reversed in some cases with the application of the proper tactics.

The other key point is that lifespan and healthspan are not independent variables; they are tightly intertwined. If you increase your muscle strength and improve your cardiorespiratory fitness, you have also reduced your risk of dying from all causes by a far greater magnitude than you could achieve by taking any cocktail of medications. The same goes for better cognitive and emotional health. The actions we take to improve our healthspan will almost always result in a longer lifespan. This is why our tactics are largely aimed at improving healthspan first; the lifespan benefits will follow.

Our tactics in Medicine 3.0 fall into five broad domains: exercise, nutrition, sleep, emotional health, and exogenous molecules, meaning drugs, hormones, or supplements.

So we will break down this thing called exercise into its most important components: strength, stability, aerobic efficiency, and peak aerobic capacity.

The best science out there says that what you eat matters, but the first-order term is how much you eat: how many calories you take into your body.

good strategy allows us to adopt new tactics and discard old ones in service of our objectives.

“Isn’t it ironic that your entire professional life is predicated around trying to make people live longer,” she mused, “yet you’re putting no energy into being less miserable, into suffering less emotionally?” She continued: “Why would you want to live longer if you’re so unhappy?” Her logic was undeniable, and it changed my whole approach to longevity.

I propose that with some unorthodox but very reasonable lifestyle changes, you can minimize the most serious threats to your lifespan and healthspan and achieve your own measure of longevity alpha.

As your own situation changes, your tactics can (and must) change, because as the great philosopher Mike Tyson once put it, “Everyone has a plan until they get punched in the mouth.” Advice George Foreman could have used.

Whiskey’s a good medicine. It keeps your muscles tender. —Richard Overton, 1906–2018

This is what we want for ourselves: to live longer with good function and without chronic disease, and with a briefer period of morbidity at the end of our lives.

Put another way, if we want to outlive our life expectancy and live better longer, we will have to work hard to earn it—through small, incremental changes.

FOXO3 belongs to a family of “transcription factors,” which regulate how other genes are expressed—meaning whether they are activated or “silenced.”

Here’s where we start to see some hope, because FOXO3 can be activated or suppressed by our own behaviors. For example, when we are slightly deprived of nutrients, or when we are exercising, FOXO3 tends to be more activated, which is what we want.

While your genome is immutable, at least for the near future, gene expression can be influenced by your environment and your behaviors. For example, a 2007 study found that older people who were put on a regular exercise program shifted to a more youthful pattern of gene expression after six months. This suggests that genetics and environment both play a role in longevity and that it may be possible to implement interventions that replicate at least some of the centenarians’ good genetic luck.

Their superpower is their ability to resist or delay the onset of chronic disease by one or two or even three decades, while also maintaining relatively good healthspan.

In the end, I think that the centenarians’ secret comes down to one word: resilience. They are able to resist and avoid cancer and cardiovascular disease, even when they have smoked for decades. They are able to maintain ideal metabolic health, often despite a lousy diet. And they resist cognitive and physical decline long after their peers succumb. It is this resilience that we want to cultivate, just as Ali prepared himself to withstand and ultimately outlast Foreman. He prepared intelligently and thoroughly, he trained for a long time before the match, and he deployed his tactics from the opening bell. He could not have lasted forever, but he made it through enough rounds that he was able to fulfill his objective and win the fight.

Scientists who play by someone else’s rules don’t have much chance of making discoveries. —Jack Horner

The job of mTOR is basically to balance an organism’s need to grow and reproduce against the availability of nutrients. When food is plentiful, mTOR is activated and the cell (or the organism) goes into growth mode, producing new proteins and undergoing cell division, as with the ultimate goal of reproduction. When nutrients are scarce, mTOR is suppressed and cells go into a kind of “recycling” mode, breaking down cellular components and generally cleaning house. Cell division and growth slow down or stop, and reproduction is put on hold to allow the organism to conserve energy.

We’re not talking about simply putting animals on Weight Watchers. Caloric restriction without malnutrition, commonly abbreviated as CR, is a precise experimental method where one group of animals (the controls) are fed ad libitum, meaning they eat as much as they want, while the experimental group or groups are given a similar diet containing all the necessary nutrients but 25 or 30 percent fewer total calories (more or less). The restricted animals are then compared against the controls.

By cleansing our cells of damaged proteins and other cellular junk, autophagy allows cells to run more cleanly and efficiently and helps make them more resistant to stress. But as we get older, autophagy declines. Impaired autophagy is thought to be an important driver of numerous aging-related phenotypes and ailments, such as neurodegeneration and osteoarthritis.

For the moment, though, let’s think about the fact that all of what we’ve talked about in this chapter, from mTOR and rapamycin to caloric restriction, points in one direction: that what we eat and how we metabolize it appear to play an outsize role in longevity. In the next chapter, we will take a much more detailed look at how metabolic disorders help to instigate and promote chronic disease.

Avoidable human misery is more often caused not so much by stupidity as by ignorance, particularly our ignorance about ourselves. —Carl Sagan

Notice that I said “metabolic dysfunction” and not “obesity,” everybody’s favorite public health bogeyman. It’s an important distinction. According to the Centers for Disease Control (CDC), more than 40 percent of the US population is obese (defined as having a BMI[*2] greater than 30), while roughly another third is overweight (BMI of 25 to 30). Statistically, being obese means someone is at greater risk of chronic disease, so a lot of attention is focused on the “obesity problem,” but I take a broader view: obesity is merely one symptom of an underlying metabolic derangement, such as hyperinsulinemia, that also happens to cause us to gain weight. But not everyone who is obese is metabolically unhealthy, and not everyone who is metabolically unhealthy is obese. There’s more to metabolic health than meets the eye.

In the 1980s, Reaven labeled this collection of related disorders “Syndrome X”—where the X factor, he eventually determined, was insulin resistance. Today we call this cluster of problems “metabolic syndrome” (or MetSyn), and it is defined in terms of the following five criteria: high blood pressure (>130/85) high triglycerides (>150 mg/dL) low HDL cholesterol (<40 mg/dL in men or <50 mg/dL in women) central adiposity (waist circumference >40 inches in men or >35 in women) elevated fasting glucose (>110 mg/dL)

Metabolism is the process by which we take in nutrients and break them down for use in the body. In someone who is metabolically healthy, those nutrients are processed and sent to their proper destinations. But when someone is metabolically unhealthy, many of the calories they consume end up where they are not needed, at best—or outright harmful, at worst.

Consider that five grams of glucose, spread out across one’s entire circulatory system, is normal, while seven grams—a teaspoon and a half—means you have diabetes. As I said, the liver is an amazing organ.

Think of fat as acting like a kind of metabolic buffer zone, absorbing excess energy and storing it safely until it is needed. If we eat extra doughnuts, those calories are stored in our subcutaneous fat; when we go on, say, a long hike or swim, some of that fat is then released for use by the muscles. This fat flux goes on continually, and as long as you haven’t exceeded your own fat storage capacity, things are pretty much fine. But if you continue to consume energy in excess of your needs, those subcutaneous fat cells will slowly fill up, particularly if little of that stored energy is being utilized. When someone reaches the limit of their capacity to store energy in their subcutaneous fat, yet they continue to take on excess calories, all that energy still has to go somewhere. The doughnuts or whatever they might be eating are probably still getting converted into fat, but now the body has to find other places to store it. It’s almost as if you have a bathtub, and you’re filling it up from the faucet. If you keep the faucet running even after the tub is full and the drain is closed (i.e., you’re sedentary), water begins spilling over the rim of the tub, flowing into places where it’s not wanted or needed, like onto the bathroom floor, into the heating vents or down the stairs. It’s the same with excess fat. As more calories flood into your subcutaneous fat tissue, it eventually reaches capacity and the surplus begins spilling over into other areas of your body: into your blood, as excess triglycerides; into your liver, contributing to NAFLD; into your muscle tissue, contributing directly to insulin resistance in the muscle (as we’ll see); and even around your heart and your pancreas (figure 4).

It doesn’t take much visceral fat to cause problems. Let’s say you are a forty-year-old man who weighs two hundred pounds. If you have 20 percent body fat, making you more or less average (50th percentile) for your age and sex, that means you are carrying 40 pounds of fat throughout your body. Even if just 4.5 pounds of that is visceral fat, you would be considered at exceptionally high risk for cardiovascular disease and type 2 diabetes, in the top 5 percent of risk for your age and sex. This is why I insist my patients undergo a DEXA scan annually—and I am far more interested in their visceral fat than their total body fat.

Insulin resistance is a term that we hear a lot, but what does it really mean? Technically, it means that cells, initially muscle cells, have stopped listening to insulin’s signals, but another way to visualize it is to imagine the cell as a balloon being blown up with air. Eventually, the balloon expands to the point where it gets more difficult to force more air inside. You have to blow harder and harder. This is where insulin comes in, to help facilitate the process of blowing air into the balloon. The pancreas begins to secrete even more insulin, to try to remove excess glucose from the bloodstream and cram it into cells. For the time being it works, and blood glucose levels remain normal, but eventually you reach a limit where the “balloon” (cells) cannot accept any more “air” (glucose).

When insulin is chronically elevated, more problems arise. Fat gain and ultimately obesity are merely one symptom of this condition, known as hyperinsulinemia. I would argue that they are hardly even the most serious symptoms: as we’ll see in the coming chapters, insulin is also a potent growth-signaling hormone that helps foster both atherosclerosis and cancer. And when insulin resistance begins to develop, the train is already well down the track toward type 2 diabetes, which brings a multitude of unpleasant consequences.

The simplest explanation is likely that our metabolism, as it has evolved over millennia, is not equipped to cope with our ultramodern diet, which has appeared only within the last century or so. Evolution is no longer our friend, because our environment has changed much faster than our genome ever could. Evolution wants us to get fat when nutrients are abundant: the more energy we could store, in our ancestral past, the greater our chances of survival and successful reproduction. We needed to be able to endure periods of time without much food, and natural selection obliged, endowing us with genes that helped us conserve and store energy in the form of fat. That enabled our distant ancestors to survive periods of famine, cold climates, and physiologic stressors such as illness and pregnancy. But these genes have proved less advantageous in our present environment, where many people in the developed world have access to almost unlimited calories.

When we metabolize fructose, along with certain other types of foods, it produces large amounts of uric acid, which is best known as a cause of gout but which has also been associated with elevated blood pressure.

At some point, our primate ancestors underwent a random genetic mutation that effectively switched on their ability to turn fructose into fat: the gene for the uricase enzyme was “silenced,” or lost. Now, when these apes consumed fructose, they generated lots of uric acid, which caused them to store many more of those fructose calories as fat. This newfound ability to store fat enabled them to survive in the colder climate. They could spend the summer gorging themselves on fruit, fattening up for the winter.

I test my patients’ levels of uric acid, not only because high levels may promote fat storage but also because it is linked to high blood pressure. High uric acid is an early warning sign that we need to address a patient’s metabolic health, their diet, or both.

On a more macro level, consuming large quantities of liquid fructose simply overwhelms the ability of the gut to handle it; the excess is shunted to the liver, where many of those calories are likely to end up as fat. I’ve seen patients work themselves into NAFLD by drinking too many “healthy” fruit smoothies, for the same reason: they are taking in too much fructose, too quickly. Thus, the almost infinite availability of liquid fructose in our already high-calorie modern diet sets us up for metabolic failure if we’re not careful (and especially if we are not physically active).

We want to intervene before a patient actually develops metabolic syndrome.

But the first thing I look for, the canary in the coal mine of metabolic disorder, is elevated insulin. As we’ve seen, the body’s first response to incipient insulin resistance is to produce more insulin. Think back to our analogy with the balloon: as it gets harder to get air (glucose) into the balloon (the cell), we have to blow harder and harder (i.e., produce more insulin). At first, this appears to be successful: the body is still able to maintain glucose homeostasis, a steady blood glucose level. But insulin, especially postprandial insulin, is already on the rise.

Yet diabetes is only one danger: Studies have found that insulin resistance itself is associated with huge increases in one’s risk of cancer (up to twelvefold), Alzheimer’s disease (fivefold), and death from cardiovascular disease (almost sixfold)—all of which underscores why addressing, and ideally preventing, metabolic dysfunction is a cornerstone of my approach to longevity.

The good news is that we have tremendous agency over this. Changing how we exercise, what we eat, and how we sleep (see Part III) can completely turn the tables in our favor. The bad news is that these things require effort to escape the default modern environment that has conspired against our ancient (and formerly helpful) fat-storing genes, by overfeeding, undermoving, and undersleeping us all.

There is some risk involved in action, there always is. But there is far more risk in failure to act. —Harry S. Truman

The scan was calibrated to detect calcification in my coronary arteries, a sign of advanced atherosclerosis. The results showed that I had a calcium “score” of 6. That sounds low, and in absolute terms it was; someone with severe disease could return a score well over 1,000. But for someone age thirty-six, it should have been zero. My score of 6 meant that I had more calcium in my coronary arteries than 75 to 90 percent of people my age. As I dug deeper into the pathology of this disease, I was dismayed to learn that it was already fairly late in the game. A calcium score is treated as a predictor of future risk, which it is, but it is also a measure of historical and existing damage. And I was already off the charts. I was only in my midthirties, but I had the arteries of a fifty-five-year-old.

While heart disease is the most prevalent age-related condition, it is also more easily prevented than either cancer or Alzheimer’s disease.

Scientists have been exploring the medical mysteries of the human heart for almost as long as poets have been probing its metaphorical depths. It is a wondrous organ, a tireless muscle that pumps blood around the body every moment of our lives. It pounds hard when we are exercising, slows down when we sleep, and even microadjusts its rate between beats, a hugely important phenomenon called heart rate variability. And when it stops, we stop.

Incredible as it is, however, our circulatory system is far from perfect—in fact, it is almost perfectly designed to generate atherosclerotic disease, just in the course of daily living. This is in large part because of another important function of our vasculature. In addition to transporting oxygen and nutrients to our tissues and carrying away waste, our blood traffics cholesterol molecules between cells.

Cholesterol is essential to life. It is required to produce some of the most important structures in the body, including cell membranes; hormones such as testosterone, progesterone, estrogen, and cortisol; and bile acids, which are necessary for digesting food. All cells can synthesize their own cholesterol, but some 20 percent of our body’s (large) supply is found in the liver, which acts as a sort of cholesterol repository, shipping it out to cells that need it and receiving it back via the circulation.

The reason they’re called high- and low-density lipoproteins (HDL and LDL, respectively) has to do with the amount of fat relative to protein that each one carries. LDLs carry more lipids, while HDLs carry more protein in relation to fat, and are therefore more dense. Also, these particles (and other lipoproteins) frequently exchange cargo with one another, which is part of what drives me crazy about labeling them “good” and “bad.” When an HDL transfers its “good cholesterol” to an LDL particle, does that cholesterol suddenly become “bad”?

Another major misconception about heart disease is that it is somehow caused by the cholesterol that we eat in our diet. According to this dated and simplistic view, eating cholesterol-rich foods causes the so-called bad cholesterol to accumulate in our blood and then build up on our artery walls, as if you poured bacon grease down the kitchen drain every time you made breakfast. Sooner or later, your sink will back up.

but most of the actual cholesterol that we consume in our food ends up being excreted out our backsides. The vast majority of the cholesterol in our circulation is actually produced by our own cells. Nevertheless, US dietary guidelines warned Americans away from consuming foods high in cholesterol for decades, and nutrition labels still inform American consumers about how much cholesterol is contained in each serving of packaged foods.

“There’s no connection whatsoever between cholesterol in food and cholesterol in blood,” Keys said in a 1997 interview. “None. And we’ve known that all along. Cholesterol in the diet doesn’t matter at all unless you happen to be a chicken or a rabbit.” It took nearly two more decades before the advisory committee responsible for the US government dietary guidelines finally conceded (in 2015) that “cholesterol is not a nutrient of concern for overconsumption.” Glad we settled that.

“What proportion of heart attacks occur in people younger than age sixty-five?” I guessed high, one in four, but I was way low. Fully half of all major adverse cardiovascular events in men (and a third of those in women), such as heart attack, stroke, or any procedure involving a stent or a graft, occur before the age of sixty-five. In men, one-quarter of all events occur before age fifty-four.

Our risk of these “events” rises steeply in the second half of our lifespan, but some scientists believe the underlying processes are set into motion in late adolescence, even as early as our teens. The risk builds throughout our lives, and the critical factor is time. Therefore it is critical that we understand how it develops, and progresses, so we can develop a strategy to try to slow or stop it.

It is not an accident that the two biggest risk factors for heart disease, smoking and high blood pressure, cause damage to the endothelium. Smoking damages it chemically, while high blood pressure does so mechanically, but the end result is endothelial harm that, in turn, leads to greater retention of LDL. As oxidized LDL accumulates, it causes still more damage to the endothelium.

Autopsy data from young people who died from accidents, homicides, or other noncardiovascular causes have revealed that as many as a third of sixteen- to twenty-year-olds already had actual atherosclerotic lesions or plaques in their coronary arteries when they died. As teenagers.

have all my patients tested for apoB regularly, and you should ask for the same test the next time you see your doctor. (Don’t be waved off by nonsensical arguments about “cost”: It’s about twenty to thirty dollars.)

I take a very hard line on lowering apoB, the particle that causes all this trouble. (In short: get it as low as possible, as early as possible.)

This is why, if you have a history of premature heart attacks in your family, you should definitely ask for an Lp(a) test. We test every single patient for Lp(a) during their first blood draw. Because elevated Lp(a) is largely genetic, the test need only be done once (and cardiovascular disease guidelines are beginning to advise a once-a-lifetime test for it anyway).

Together, our stories illustrate three blind spots of Medicine 2.0 when it comes to dealing with atherosclerotic disease: first, an overly simplistic view of lipids that fails to understand the importance of total lipoprotein burden (apoB) and how much one needs to reduce it in order to truly reduce risk; second, a general lack of knowledge about other bad actors such as Lp(a); and third, a failure to fully grasp the lengthy time course of atherosclerotic disease, and the implications this carries if we seek true prevention.

Once you establish the central importance of apoB, the next question becomes, By how much does one need to lower it (or its proxy LDL-C) to achieve meaningful risk reduction? The various treatment guidelines specify target ranges for LDL-C, typically 100 mg/dL for patients at normal risk, or 70 mg/dL for high-risk individuals. In my view, this is still far too high. Simply put, I think you can’t lower apoB and LDL-C too much, provided there are no side effects from treatment. You want it as low as possible.

Monounsaturated fats, found in high quantities in extra virgin olive oil, macadamia nuts, and avocados (among other foods), do not have this effect, so I tend to push my patients to consume more of these, up to about 60 percent of total fat intake. The point is not necessarily to limit fat overall but to shift to fats that promote a better lipid profile.

Statins are far and away the most prescribed class of drugs for lipid management, but there are several other options that might be right for a given individual, and often we need to combine classes of drugs, so it’s not uncommon for a patient to take two lipid-lowering drugs that operate via distinct mechanisms. These are typically thought of as “cholesterol-lowering” medications, but I think we are better served to think about them in terms of increasing apoB clearance, enhancing the body’s ability to get apoBs out of circulation. That’s really our goal. Mostly this is done by amplifying the activity of LDL receptors (LDLR) in the liver, which absorb cholesterol from the bloodstream.

Not everyone can take statins comfortably; about 5 percent of patients experience deal-breaking side effects, most notably statin-related muscle pain.

For every seven people who are put on a statin at this early stage, we could potentially save one life. The reason for this is simple math: risk is proportional to apoB exposure over time. The sooner we lower apoB exposure, thus lowering risk, the more the benefits compound over time—and the greater our overall risk reduction.

and more importantly seeks to identify and eliminate the primary causative agent in the disease process: apoB.

Once you understand that apoB particles—LDL, VLDL, Lp(a)—are causally linked to ASCVD, the game completely changes. The only way to stop the disease is to remove the cause, and the best time to do that is now.

Still struggling with this idea? Consider the following example. We know that smoking is causally linked to lung cancer. Should we tell someone to stop smoking only after their ten-year risk of lung cancer reaches a certain threshold? That is, do we think it’s okay for people to keep smoking until they are sixty-five and then quit? Or should we do everything we can to help young people, who have maybe just picked up the habit, quit altogether? When viewed this way, the answer is unambiguous. The sooner you cut the head off the snake, the lower the risk that it will bite you.

I want to knock someone’s apoB concentration down to 20 or 30 mg/dL, about where it would be for a child.

You may have to fight a battle more than once to win it. —Margaret Thatcher

Despite well over $100 billion spent on research via the National Cancer Institute, plus many billions more from private industry and public charities—despite all the pink ribbons and yellow bracelets, and literally millions of published papers on the PubMed database—cancer is the second leading cause of death in the United States, right behind heart disease. Together, these two conditions account for almost one in every two American deaths.

By the time cancer is detected, however, it has probably already been progressing for years and possibly decades.

I feel that immunotherapy, in particular, has enormous promise.

Third, and perhaps most importantly, we need to try to detect cancer as early as possible so that our treatments can be deployed more effectively. I advocate early, aggressive, and broad screening for my patients—such as colonoscopy (or other colorectal cancer screening) at age forty, as opposed to the standard recommendation of forty-five or fifty—because the evidence is overwhelming that it’s much easier to deal with most cancers in their early stages. I am also cautiously optimistic about pairing these tried-and-true staples of cancer screening with emerging methods, such as “liquid biopsies,” which can detect trace amounts of cancer-cell DNA via a simple blood test.

So not only is breast cancer genetically distinct from colon cancer (as the researchers expected), but no two breast cancer tumors are very much alike. If two women have breast cancer, at the same stage, their tumor genomes are likely to be very different from each other. Therefore, it would be difficult if not impossible to devise one treatment for both women based on the genetic profile of their tumors. Rather than revealing the shape of the forest, then, The Cancer Genome Atlas merely dragged us deeper into the maze of the trees.

If we want to reduce cancer mortality by a significant amount, we must do a better job of preventing, detecting, and treating metastatic cancers.

Traditional chemotherapy occupies a fuzzy region between poison and medicine; the mustard gas used as a weapon during World War I was a direct precursor to some of the earliest chemotherapy agents, some of which are still in use. These drugs attack the replicative cycle of cells, and because cancer cells are rapidly dividing, the chemo agents harm them more severely than normal cells. But many important noncancerous cells are also dividing frequently, such as those in the lining of the mouth and gut, the hair follicles, and the nails, which is why typical chemotherapy agents cause side effects like hair loss and gastrointestinal misery. Meanwhile, as cancer researcher Robert Gatenby points out, those cancer cells that do manage to survive chemotherapy often end up acquiring mutations that make them stronger, like cockroaches that develop resistance to insecticides.

In fact, turning glucose into lactate creates so many extra molecules that the authors argued that the relatively small amount of energy it produces may actually be the “by-product.”

The Warburg effect, also known as anaerobic glycolysis, turns the same amount of glucose into a little bit of energy and a whole lot of chemical building blocks—which are then used to build new cells rapidly. Thus, the Warburg effect is how cancer cells fuel their own proliferation.

The American Cancer Society reports that excess weight is a leading risk factor for both cancer cases and deaths, second only to smoking.

Globally, about 12 to 13 percent of all cancer cases are thought to be attributable to obesity. Obesity itself is strongly associated with thirteen different types of cancers, including pancreatic, esophageal, renal, ovarian, and breast cancers, as well as multiple myeloma (see figure 7). Type 2 diabetes also increases the risk of certain cancers, by as much as double in some cases (such as pancreatic and endometrial cancers). And extreme obesity (BMI ≥ 40) is associated with a 52 percent greater risk of death from all cancers in men, and 62 percent in women.

Thus, insulin acts as a kind of cancer enabler, accelerating its growth.

What I am saying is that we don’t want to be anywhere on that spectrum of insulin resistance to type 2 diabetes, where our cancer risk is clearly elevated. To me, this is the low-hanging fruit of cancer prevention, right up there with quitting smoking. Getting our metabolic health in order is essential to our anticancer strategy.

From that crude drawing on a napkin, a study was born. Published in Nature in 2018, with Mukherjee and Cantley as senior authors, the study found that a combination of a ketogenic diet and PI3K inhibitors improved the responses to treatment of mice that had been implanted with human cancer tumors. The results are important because they show not only that a cancer cell’s metabolism is a valid target for therapy but that a patient’s metabolic state can affect the efficacy of a drug. In this case, the animals’ ketogenic diet seemed to synergize with what was otherwise a somewhat disappointing treatment, and together they proved to be far more powerful than either one alone.

Other types of dietary interventions have been found to help improve the effectiveness of chemotherapy, while limiting its collateral damage to healthy tissues. Work by Valter Longo of the University of Southern California and others has found that fasting, or a fasting-like diet, increases the ability of normal cells to resist chemotherapy, while rendering cancer cells more vulnerable to the treatment. It may seem counterintuitive to recommend fasting to cancer patients, but researchers have found that it caused no major adverse events in chemotherapy patients, and in some cases it may have improved the patients’ quality of life. A randomized trial in 131 cancer patients undergoing chemotherapy found that those who were placed on a “fasting-mimicking diet” (basically, a very low-calorie diet designed to provide essential nutrients while reducing feelings of hunger) were more likely to respond to chemotherapy and to feel better physically and emotionally. This flies in the face of traditional practice, which is to try to get patients on chemotherapy to eat as much as they can tolerate, typically in the form of high-calorie and even high-sugar diets. The American Cancer Society suggests using ice cream “as a topping on cake.” But the results of these studies suggest that maybe it’s not such a good idea to increase the level of insulin in someone who has cancer. More studies need to be done, but the working hypothesis is that because cancer cells are so metabolically greedy, they are therefore more vulnerable than normal cells to a reduction in nutrients—or more likely, a reduction in insulin, which activates the PI3K pathway essential to the Warburg effect.

This study and the Mukherjee-Cantley study we discussed earlier also point toward another important takeaway from this chapter, which is that there is rarely only one way to treat a cancer successfully.

One very promising technique is called adoptive cell therapy (or adoptive cell transfer, ACT). ACT is a class of immunotherapy whereby supplemental T cells are transferred into a patient, like adding reinforcements to an army, to bolster their ability to fight their own tumor.

Each of these approaches has advantages and disadvantages,[*4] but the interesting part is that ACT effectively means designing a new, customized anticancer drug for each individual patient.

One striking feature of immune-based cancer treatment is that when it works, it really works. It is not uncommon for a patient with metastatic cancer to enter remission after chemotherapy. The problem is that it virtually never lasts. The cancer almost always comes back in some form. But when patients do respond to immunotherapy, and go into complete remission, they often stay in remission. Between 80 and 90 percent of so-called complete responders to immunotherapy remain disease-free fifteen years out.

The final and perhaps most important tool in our anticancer arsenal is early, aggressive screening. This remains a controversial topic, but the evidence is overwhelming that catching cancer early is almost always net beneficial.

When cancers are detected early, in stage I, survival rates skyrocket. This is partly because of simple math: these earlier-stage cancers comprise fewer total cancerous cells, with fewer mutations, and thus are more vulnerable to treatment with the drugs that we do have, including some immunotherapies. I would go so far as to argue that early detection is our best hope for radically reducing cancer mortality.

My bottom line is that it is far better to screen early than risk doing it too late. Think asymmetric risk: It’s possible that not screening early and frequently enough is the most dangerous option.

The implications of this, I think, are seismic: if liquid biopsies deliver on their promise, we could completely flip the time line of cancer so that we are routinely intervening early, when we have a chance of controlling or even eliminating the cancer—rather than the way we typically do it now, coming in at a late stage, when the odds are already stacked against the patient, and hoping for a miracle.

The only modifiable risks that really stand out in the data are smoking, insulin resistance, and obesity (all to be avoided)—and maybe pollution (air, water, etc.), but the data here are less clear.

If the first rule of cancer is “Don’t get cancer,” the second rule is “Catch it as soon as possible.”

The greatest obstacle to discovery is not ignorance—it is the illusion of knowledge. —Daniel J. Boorstin

This is not all that uncommon in medicine, where the index case for a particular disease turns out to be the exception rather than the rule; extrapolating from this one case can lead to problems and misunderstanding down the road. At the same time, if Auguste Deter’s illness had appeared when she was seventy-five instead of fifty, then perhaps it might not have seemed remarkable at all.

Some scientists believe there may be something about menopause, and the abrupt decline in hormonal signaling, that sharply increases the risk of neurodegeneration in older women. In particular, it appears that a rapid drop in estradiol in women with an e4 allele is a driver of risk; that, in turn, suggests a possible role for perimenopausal hormone replacement therapy in these women.

The end result is that women have a greater age-adjusted risk of Alzheimer’s, as well as faster rates of disease progression overall, regardless of age and educational level.

Olfactory neurons are among the first to be affected by Alzheimer’s disease.

One reason why Alzheimer’s and related dementias can be so tricky to diagnose is that our highly complex brains are adept at compensating for damage, in a way that conceals these early stages of neurodegeneration. When we have a thought or a perception, it’s not just one neural network that is responsible for that insight, or that decision, but many individual networks working simultaneously on the same problem, according to Francisco Gonzalez-Lima, a behavioral neuroscientist at the University of Texas in Austin. These parallel networks can reach different conclusions, so when we use the expression “I am of two minds about something,” that is not scientifically inaccurate. The brain then picks the most common response. There is redundancy built into the system.

The more of these networks and subnetworks that we have built up over our lifetime, via education or experience, or by developing complex skills such as speaking a foreign language or playing a musical instrument, the more resistant to cognitive decline we will tend to be. The brain can continue functioning more or less normally, even as some of these networks begin to fail. This is called “cognitive reserve,” and it has been shown to help some patients to resist the symptoms of Alzheimer’s disease. It seems to take a longer time for the disease to affect their ability to function. “People that have Alzheimer’s disease and are very cognitively engaged, and have a good backup pathway, they’re not going to decline as quickly,” Richard says.

There is a parallel concept known as “movement reserve” that becomes relevant with Parkinson’s disease. People with better movement patterns, and a longer history of moving their bodies, such as trained or frequent athletes, tend to resist or slow the progression of the disease as compared to sedentary people. This is also why movement and exercise, not merely aerobic exercise but also more complex activities like boxing workouts, are a primary treatment/prevention strategy for Parkinson’s. Exercise is the only intervention shown to delay the progression of Parkinson’s.

The brain is a greedy organ. It makes up just 2 percent of our body weight, yet it accounts for about 20 percent of our total energy expenditure. Its eighty-six billion neurons each have between one thousand and ten thousand synapses connecting them to other neurons or target cells, creating our thoughts, our personalities, our memories, and the reasoning behind both our good and bad decisions. There are computers that are bigger and faster, but no machine yet made by man can match the brain’s ability to intuit and learn, much less feel or create. No computer possesses anything approaching the multidimensionality of the human self. Where a computer is powered by electricity, the beautiful machine that is the human brain depends on a steady supply of glucose and oxygen, delivered via a huge and delicate network of blood vessels. Even slight disruptions to this vascular network can result in a crippling or even fatal stroke.

The brain is the last thing to shut off.

Having type 2 diabetes doubles or triples your risk of developing Alzheimer’s disease, about the same as having one copy of the APOE e4 gene. On a purely mechanistic level, chronically elevated blood glucose, as seen in type 2 diabetes and prediabetes/insulin resistance, can directly damage the vasculature of the brain. But insulin resistance alone is enough to elevate one’s risk.

All this suggests that metabolic and vascular causes of dementia may be somewhat overlapping, just as patients with insulin resistance are also prone to vascular disease. And it tells us that with high-risk patients like Stephanie, we need to pay special attention to their metabolic health.

There is some evidence that supplementation with the omega-3 fatty acid DHA, found in fish oil, may help maintain brain health, especially in e4/e4 carriers. Higher doses of DHA may be required because of e4-induced metabolic changes and dysfunction of the blood-brain barrier.

This is also one area where a ketogenic diet may offer a real functional advantage: when someone is in ketosis, their brain relies on a mix of ketones and glucose for fuel. Studies in Alzheimer’s patients find that while their brains become less able to utilize glucose, their ability to metabolize ketones does not decline. So it may make sense to try to diversify the brain’s fuel source from only glucose to both glucose and ketones. A systematic review of randomized controlled trials found that ketogenic therapies improved general cognition and memory in subjects with mild cognitive impairment and early-stage Alzheimer’s disease. Think of it as a flex-fuel strategy.

endurance exercise produces factors that directly target regions of the brain responsible for cognition and memory. It also helps lower inflammation and oxidative stress. Strength training is likely just as important. A study looking at nearly half a million patients in the United Kingdom found that grip strength, an excellent proxy for overall strength, was strongly and inversely associated with the incidence of dementia (see figure 8).

Sleep is also a very powerful tool against Alzheimer’s disease, as we’ll see in chapter 16. Sleep is when our brain heals itself; while we are in deep sleep our brains are essentially “cleaning house,” sweeping away intracellular waste that can build up between our neurons. Sleep disruptions and poor sleep are potential drivers of increased risk of dementia. If poor sleep is accompanied by high stress and elevated cortisol levels, as in Stephanie’s case, that acts almost as a multiplier of risk, as it contributes to insulin resistance and damaging the hippocampus at the same time.

Another somewhat surprising risk factor that has emerged is hearing loss. Studies have found that hearing loss is clearly associated with Alzheimer’s disease, but it’s not a direct symptom. Rather, it seems hearing loss may be causally linked to cognitive decline, because folks with hearing loss tend to pull back and withdraw from interactions with others. When the brain is deprived of inputs—in this case auditory inputs—it withers. Patients with hearing loss miss out on socializing, intellectual stimulation, and feeling connected; prescribing them hearing aids may help relieve some symptoms. This is just a hypothesis for the moment, but it is being tested right now in a clinical trial called ACHIEVE (Aging and Cognitive Health Evaluation in Elders) that is currently ongoing.

Another surprising intervention that may help reduce systemic inflammation, and possibly Alzheimer’s disease risk, is brushing and flossing one’s teeth. (You heard me: Floss.) There is a growing body of research linking oral health, particularly the state of one’s gum tissue, with overall health. Researchers have found that one pathogen in particular, a microbe called P. gingivalis that commonly causes gum disease, is responsible for large increases in levels of inflammatory markers such as IL-6. Even stranger, P. gingivalis has also shown up inside the brains of patients with Alzheimer’s disease, although scientists are not certain that this bacterium is directly causing dementia, notes Dr. Patricia Corby, a professor of dental health at New York University. Nevertheless, the association is too strong to be ignored. (Also, better oral health correlates strongly with better overall health, particularly in terms of cardiovascular disease risk, so I pay much more attention to flossing and gum health than I used to.)

Absorb what is useful, discard what is useless, and add what is specifically your own. —Bruce Lee

“Cancer, like insanity, seems to increase with the progress of civilization.”

The conundrum we face is that our environment has changed dramatically over the last century or two, in almost every imaginable way—our food supply and eating habits, our activity levels, and the structure of our social networks—while our genes have scarcely changed at all. We saw a classic example of this in chapter 6, with the changing role that fructose has played in our diet. Long ago, when we consumed fructose mainly in the form of fruit and honey, it enabled us to store energy as fat to survive cold winters and periods of scarcity. Fructose was our friend. Now fructose is vastly overabundant in our diet, too much of it in liquid form, which disrupts our metabolism and our overall energy balance. We can easily take in far more fructose calories than our bodies can safely handle.

Our genes no longer match our environment. Thus, we must be cunning in our tactics if we are to adapt and thrive in this new and hazardous world.

Recognizing the danger points is the first step in developing good tactics.

We approach our tactics the same way, zooming in from the vague and general to the specific and targeted. We use data and intuition to figure out where to focus our efforts, and feedback to determine what is and isn’t working. And seemingly small tweaks can yield a significant advantage if compounded over time.

Our two most complex tactical domains are nutrition and exercise, and I find that most people need to make changes in both—rarely just one or the other. When I evaluate new patients, I’m always asking three key questions: a. Are they overnourished or undernourished? That is, are they taking in too many or too few calories? b. Are they undermuscled or adequately muscled? c. Are they metabolically healthy or not?

But the action part is their responsibility; not much of this stuff is easy. It requires them to change their habits and do the work.

We adapt our tactics on the basis of our changing needs and our changing understanding of the best science out there. Our only goal is to live longer and live better—to outlive. To do that, we must rewrite the narrative of decline that so many others before us have endured and figure out a plan to make each decade better than the one before.

Exercise The Most Powerful Longevity Drug I never won a fight in the ring; I always won in preparation. —Muhammad Ali

Even a little bit of daily activity is much better than nothing. Going from zero weekly exercise to just ninety minutes per week can reduce your risk of dying from all causes by 14 percent. It’s very hard to find a drug that can do that.

It turns out that peak aerobic cardiorespiratory fitness, measured in terms of VO2 max, is perhaps the single most powerful marker for longevity. VO2 max represents the maximum rate at which a person can utilize oxygen. This is measured, naturally, while a person is exercising at essentially their upper limit of effort. (If you’ve ever had this test done, you will know just how unpleasant it is.) The more oxygen your body is able to use, the higher your VO2 max.

The fitter I am, the more oxygen I can consume to make ATP, and the faster I can run up that hill.

The higher someone’s VO2 max, the more oxygen they can consume to make ATP, and the faster they can ride or run—in short, the more they can do.

Thus, poor cardiorespiratory fitness carries a greater relative risk of death than smoking.

But I can say with a very high degree of certainty that having a higher VO2 max is better for your overall health and longevity than having a lower VO2 max. Period. Even better news, for our purposes, is that VO2 max can be increased via training. We can move the needle a lot on this measure of fitness, as we’ll see.

Subjects with low muscle strength were at double the risk of death, while those with low muscle mass and/or low muscle strength, plus metabolic syndrome, had a 3 to 3.33 times greater risk of all-cause mortality.

It’s pretty much the same story we saw with VO2 max: The fitter you are, the lower your risk of death. Again, there is no other intervention, drug or otherwise, that can rival this magnitude of benefit. Exercise is so effective against diseases of aging—the Horsemen—that it has often been compared to medicine.

The list goes on and on, but simply put, exercise helps the human “machine” perform far better for longer.

Muscle helps us survive old age.

Just as with VO2 max, it is important to maintain muscle mass at all costs.

We need to adopt a similar approach to aging, I decided: each of us needs to be training for the Centenarian Decathlon.

Hike 1.5 miles on a hilly trail. Get up off the floor under your own power, using a maximum of one arm for support. Pick up a young child from the floor. Carry two five-pound bags of groceries for five blocks. Lift a twenty-pound suitcase into the overhead compartment of a plane. Balance on one leg for thirty seconds, eyes open. (Bonus points: eyes closed, fifteen seconds.) Have sex. Climb four flights of stairs in three minutes. Open a jar. Do thirty consecutive jump-rope skips.

The beauty of the Centenarian Decathlon is that it is broad yet unique to each individual. Nor is it limited to ten events; for most people it ends up being more, depending on their goals. My version of the Decathlon is tailored to my own particular interests, such as swimming and archery. It’s also fairly aggressive, I admit, reflecting the importance of a high level of fitness in my life. So I would probably add in some of the following events: Swim half a mile in twenty minutes. Walk with a thirty-pound dumbbell in each hand for one minute. Draw back and fire a fifty-pound compound bow. Do five pull-ups. Climb ninety steps in two minutes (VO2 max = 32). Dead-hang for one minute. Drive a race car within 5 to 8 percent of the pace I can do so today. Hike with a twenty-pound backpack for an hour. Carry my own luggage. Walk up a steep hill.

By fixing our aim on the Centenarian Decathlon, we can make every decade between now and then better as well.

As Centenarian Decathletes, we are no longer training for a specific event, but to become a different sort of athlete altogether: an athlete of life.

is impossible to produce superior performance unless you do something different from the majority. —Sir John Templeton

For our purposes, we are interested in two particular regions of this continuum: long, steady endurance work, such as jogging or cycling or swimming, where we are training in what physiologists call zone 2, and maximal aerobic efforts, where VO2 max comes into play.

I am convinced that it is impossible to be healthy without also having healthy mitochondria, which is why I place a great deal of emphasis on long, steady endurance training in zone 2.

Zone 2 is more or less the same in all training models: going at a speed slow enough that one can still maintain a conversation but fast enough that the conversation might be a little strained. It translates to aerobic activity at a pace somewhere between easy and moderate.

Typically, someone working at a lower relative intensity will be burning more fat, while at higher intensities they would rely more on glucose. The healthier and more efficient your mitochondria, the greater your ability to utilize fat, which is by far the body’s most efficient and abundant fuel source. This ability to use both fuels, fat and glucose, is called “metabolic flexibility,” and it is what we want: in chapters 6 and 7, we saw how the relentless accumulation and spillover of fat drives conditions such as diabetes and cardiovascular disease. Healthy mitochondria (fostered by zone 2 training) help us keep this fat accumulation in check.

effort that we can maintain without accumulating lactate. We still produce it, but we’re able to match production with clearance. The more efficient our mitochondrial “engine,” the more rapidly we can clear lactate, and the greater effort we can sustain while remaining in zone 2. If we are “feeling the burn” in this type of workout, then we are likely going too hard, creating more lactate than we can eliminate.

It seems unjust, but the people who most need to burn their fat, the people with the most of it, are unable to unlock virtually any of that fat to use as energy, while the lean, well-trained professional athletes are able to do so easily because they possess greater metabolic flexibility (and healthier mitochondria).[*2]

I think of zone 2 as akin to building a foundation for a house. Most people will never see it, but it is nevertheless important work that helps support virtually everything else we do, in our exercise regimen and in our lives.

But if you really want to raise your VO2 max, you need to train this zone more specifically. Typically, for patients who are new to exercising, we introduce VO2 max training after about five or six months of steady zone 2 work.

It is important that your goals reflect your own priorities—the activities that you enjoy, and what you want to be able to accomplish in your later decades. The more active you want or plan to be as you age, the more you need to train for it now.

Once maximal oxygen consumption or VO2 max drops below a certain level (typically about 18 ml/kg/min in men, and 15 in women), it begins to threaten your ability to live on your own. Your engine is beginning to fail.

Our goal is to become elite athletes of aging.

The payoff is that increasing your VO2 max makes you functionally younger. One study found that boosting elderly subjects’ VO2 max by 6 ml/kg/min, or about 25 percent, was equivalent to subtracting twelve years from their age.

The beauty of this is that VO2 max can always be improved by training, no matter how old you are.

The tried-and-true formula for these intervals is to go four minutes at the maximum pace you can sustain for this amount of time—not an all-out sprint, but still a very hard effort. Then ride or jog four minutes easy, which should be enough time for your heart rate to come back down to below about one hundred beats per minute. Repeat this four to six times and cool down.

• Entreno

The good news, I suppose, is that you don’t need to spend very much time in the pain cave. Unless you are training to be competitive in elite endurance sports like cycling, swimming, running, triathlon, or cross-country skiing, a single workout per week in this zone will generally suffice.

Training and maintaining a high level of aerobic fitness, and doing it now, is essential to preserving this range of function in your later years.

The sad fact is that our muscle mass begins to decline as early as our thirties. An eighty-year-old man will have about 40 percent less muscle tissue (as measured by cross section of the vastus lateralis, aka the “quad” muscle of the thigh) than he did at twenty-five. But muscle mass may be the least important metric here. According to Andy Galpin, a professor of kinesiology at California State University, Fullerton, and one of the foremost authorities on strength and performance, we lose muscle strength about two to three times more quickly than we lose muscle mass. And we lose power (strength x speed) two to three times faster than we lose strength. This is because the biggest single change in the aging muscle is the atrophy of our fast twitch or type 2 muscle fibers. Ergo, our training must be geared towards improving these with heavy resistance training. Daily life and zone 2 endurance work may be enough to prevent atrophy of type 1 fibers—but unless you are working against significant resistance, your type 2 muscle fibers will wither away. It takes much less time to lose muscle mass and strength than to gain it, particularly if we are sedentary. Even if someone has been training diligently, a short period of inactivity can erase many of those gains. If that inactivity stems from a fall or a broken bone, and lasts longer than a few days, it can often kick off a steep decline from which we may never fully recover, which is pretty much what happened with Sophie.

If someone is sedentary and consuming excess calories, muscle loss accelerates, because one of the primary destinations of fat spillover is into muscle.

The fact is that bone density diminishes on a parallel trajectory to muscle mass, peaking as early as our late twenties before beginning a slow, steady decline.

When we detect low or rapidly declining BMD in a middle-aged person, we use the following four strategies: Optimize nutrition, focusing on protein and total energy needs (see nutrition chapters). Heavy loading-bearing activity. Strength training, especially with heavy weights, stimulates the growth of bone—more than impact sports such as running (though running is better than swimming/cycling). Bones respond to mechanical tension and estrogen is the key hormone in mediating the mechanical signal (weight bearing) to a chemical one telling the body to lay down more bone. HRT, if indicated. Drugs to increase BMD, if indicated.

I think of strength training as a form of retirement saving. Just as we want to retire with enough money saved up to sustain us for the rest of our lives, we want to reach older age with enough of a “reserve” of muscle (and bone density) to protect us from injury and allow us to continue to pursue the activities that we enjoy.

This frames how I view strength training in general. It’s largely about improving your ability to carry things.

As great as rucking is, it’s not the only thing I rely on to build my strength. Fundamentally I structure my training around exercises that improve the following: Grip strength, how hard you can grip with your hands, which involves everything from your hands to your lats (the large muscles on your back). Almost all actions begin with the grip. Attention to both concentric and eccentric loading for all movements, meaning when our muscles are shortening (concentric) and when they are lengthening (eccentric). In other words, we need to be able to lift the weight up and put it back down, slowly and with control. Rucking down hills is a great way to work on eccentric strength, because it forces you to put on the “brakes.” Pulling motions, at all angles from overhead to in front of you, which also requires grip strength (e.g., pull-ups and rows). Hip-hinging movements, such as the deadlift and squat, but also step-ups, hip-thrusters, and countless single-leg variants of exercises that strengthen the legs, glutes, and lower back.

The loftier the building, the deeper the foundation must be laid. —Thomas à Kempis

In sum, stability lets us create the most force in the safest manner possible, connecting our body’s different muscle groups with much less risk of injury to our joints, our soft tissue, and especially our vulnerable spine. The goal is to be strong, fluid, flexible, and agile as you move through your world.

The point of DNS is to retrain our bodies—and our brains—in those patterns of perfect movement that we learned as little kids.

“DNS beautifully integrates with all the good work you are already doing—it’s like a software upgrade for anything you are doing.”

while strength training and aerobic conditioning are relatively straightforward, everyone has very different issues with regard to stability. Thus, it’s impossible to give a one-size-fits-all prescription for everyone.

If you’d like to know more after you’ve read this chapter, I suggest visiting the websites for DNS (www.rehabps.com) and the Postural Restoration Institute (PRI) (www.posturalrestoration.com),

The link between the body, the mind, and the breath is not new to anyone who has done more than a few Pilates or yoga classes or practiced meditation. In these practices, the breath is our anchor, our touchstone, our timekeeper. It both reflects our mental state and affects it. If our breathing is off, it can disrupt our mental equilibrium, creating anxiety and apprehension; but anxiety can also worsen any breathing issues we might have. This is because deep, steady breathing activates the calming parasympathetic nervous system, while rapid or ragged breathing triggers its opposite, the sympathetic nervous system, part of the fight-or-flight response.

Yet breathing is also important to stability and movement, and even to strength. Poor or disordered breathing can affect our motor control and make us susceptible to injury, studies have found.

It’s extremely subtle, but the way in which someone breathes gives tremendous insight to how they move their body and, more importantly, how they stabilize their movements.

The idea behind breath training is that proper breathing affects so many other physical parameters: rib position, neck extension, the shape of the spine, even the position of our feet on the ground. The way in which we breathe reflects how we interact with the world. “Making sure that your breath can be wide and three-dimensional and easy is vital for creating good, efficient, coordinated movement,” Beth says.

The larger point is that someone’s breathing style gives us insight into their broader stability strategy, the set of patterns that they have evolved over the years to help them get by in the physical world. All of us have these strategies, and 95 percent of the time, in the course of daily life, they work fine. But once you add different stressors, such as speed, weight, and novelty or unfamiliarity (e.g., stepping off a stair in the dark), then those strategies, those instinctive physical reactions, can create problems. And if our respiration is also taxed, those other problems will be magnified.

Our toes are crucial to walking, running, lifting, and, most importantly, decelerating or lowering. The big toe especially is necessary for the push-off in every stride. Lack of big-toe extension can cause gait dysfunction and can even be a limiting factor in getting up off the floor unassisted as we age. If toe strength is compromised, everything up the chain is more vulnerable—ankle, knee, hip, spine.

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Try to lift all ten toes off the ground and spread them as wide as you can. Now try to put just your big toe back on the floor, while keeping your other toes lifted. Trickier than you’d think, right? Now do the opposite: keep four toes on the floor and lift only your big toe. Then lift all five toes, and try to drop them one by one, starting with your big toe. (You get the idea.)

One of the goals of stability training is to regain mental control, conscious or not, over key muscles and body parts.

key test in our movement assessment is to have our patients stand with one foot in front of the other and try to balance. Now close your eyes and see how long you can hold the position. Ten seconds is a respectable time; in fact, the ability to balance on one leg at ages fifty and older has been correlated with future longevity, just like grip strength. (Pro tip: balancing becomes a lot easier if you first focus on grounding your feet, as described above.)

That’s what stability is about: safe and powerful transmission of force through muscles and bones, and not joints or spinal hinge points.

Slow down, go fast. It’s the same, I think, with learning stability.

I see that a lot among my own patients: they trade health for wealth.

Religion is a culture of faith; science is a culture of doubt. —Richard Feynman

Which brings us to my final quibble about the world of nutrition and diets, which is the extreme tribalism that seems to prevail there. Low-fat, vegan, carnivore, Paleo, low-carb, or Atkins—every diet has its zealous warriors who will proclaim the superiority of their way of eating over all others until their dying breath, despite a total lack of conclusive evidence.

Instead of diet, we should be talking about nutritional biochemistry. That takes it out of the realm of ideology and religion—and above all, emotion—and places it firmly back into the realm of science. We can think of this new approach as Nutrition 3.0: scientifically rigorous, highly personalized, and (as we’ll see) driven by feedback and data rather than ideology and labels. It’s not about telling you what to eat; it’s about figuring out what works for your body and your goals—and, just as important, what you can stick to.

The correlation between poor metabolic health and being overnourished and undermuscled is very high. Hence, for a majority of patients the goal is to reduce energy intake while adding lean mass. This means we need to find ways to get them to consume fewer calories while also increasing their protein intake, and to pair this with proper exercise. This is the most common problem we are trying to solve around nutrition.

So any dietary intervention that compromises muscle, or lean body mass, is a nonstarter—for both the under- and overnourished groups.

Nutrition is relatively simple, actually. It boils down to a few basic rules: don’t eat too many calories, or too few; consume sufficient protein and essential fats; obtain the vitamins and minerals you need; and avoid pathogens like E. coli and toxins like mercury or lead. Beyond that, we know relatively little with complete certainty. Read that sentence again, please.

Efficacy tests how well the intervention works under perfect conditions and adherence (i.e., if one does everything exactly as prescribed). Effectiveness tests how well the intervention works under real-world conditions, in real people.

There are two issues at play here. The first is compliance: how well can you stick to the diet? That differs for everyone; we all have different behaviors and thought patterns around food. The second issue is how a given diet affects you, with your individual metabolism and other risk factors. Yet these are too often ignored, and we end up with generalizations about how diets “don’t work.” What that really means is that diet X or diet Y doesn’t work for everyone.

My doctor told me to stop having intimate dinners for four. Unless there are three other people. —Orson Welles

Once you strip away the labels and the ideology, almost all diets rely on at least one of the following three strategies to accomplish this: CALORIC RESTRICTION, or CR: eating less in total, but without attention to what is being eaten or when it’s being eaten DIETARY RESTRICTION, or DR: eating less of some particular element(s) within the diet (e.g., meat, sugar, fats) TIME RESTRICTION, or TR: restricting eating to certain times, up to and including multiday fasting

One not uncommon scenario that we see with TR is that a person loses weight on the scale, but their body composition alters for the worse: they lose lean mass (muscle) while their body fat stays the same or even increases.

I may be starting to sound like a broken record, but it should be obvious by now that many of the problems we want to address or avoid stem from consuming calories in excess of what we can use or safely store. If we take in more energy than we require, the surplus ends up in our adipose tissue, one way or another. If this imbalance continues, we exceed the capacity of our “safe” subcutaneous fat tissue, and excess fat spills over into our liver, our viscera, and our muscles, as we discussed in chapter 6.

But sometimes science tells us more when an experiment “fails” than when it yields the expected results,

Upshot: the quality of your diet may matter as much as the quantity.

Avoiding diabetes and related metabolic dysfunction—especially by eliminating or reducing junk food—is very important to longevity. There appears to be a strong link between calories and cancer, the leading cause of death in the control monkeys in both studies. The CR monkeys had a 50 percent lower incidence of cancer. The quality of the food you eat could be as important as the quantity. If you’re eating the SAD, then you should eat much less of it. Conversely, if your diet is high quality to begin with, and you are metabolically healthy, then only a slight degree of caloric restriction—or simply not eating to excess—can still be beneficial.

The monkeys teach us that if you are metabolically healthy and not over-nourished, like the NIH animals, then avoiding a crap diet may be all you need.

We need to erect walls around what we can and cannot (or should not) eat.

One reason carbohydrate restriction is so effective for many people is that it tends to reduce appetite as well as food choices. But some people have a harder time maintaining it than others.

If you cut out carbohydrates altogether but overdo it on the Wagyu steaks and bacon, you will fairly easily find yourself in a state of caloric excess.

A more significant issue with DR is that everyone’s metabolism is different. Some people will lose tremendous amounts of weight and improve their metabolic markers on a low-carbohydrate or ketogenic diet, while others will actually gain weight and see their lipid markers go haywire—on the exact same diet. Conversely, some people might lose weight on a low-fat diet, while others will gain weight. I have seen this happen time and again in my own practice, where similar diets yield very different outcomes, depending on the individual.

Type 2 diabetes is a condition of impaired carbohydrate metabolism, after all.

had to remind myself of what Steve Rosenberg used to say when a patient’s cancer progressed despite treatment: The patient has not failed the treatment; the treatment has failed the patient. These patients needed a different treatment.

Nutrition 3.0–style, is not picking which evil foods we’re eliminating. Rather, it’s finding the best mix of macronutrients for our patient—coming up with an eating pattern that helps them achieve their goals, in a way that they can sustain. This is a tricky balancing act, and it requires us (once again) to forget about labels and viewpoints and drill down into nutritional biochemistry. The way we do this is by manipulating our four macronutrients: alcohol, carbohydrates, protein, and fat. How well do you tolerate carbohydrates? How much protein do you require? What sorts of fats suit you best? How many calories do you require each day? What is the optimal combination for you?

Alcohol serves no nutritional or health purpose but is a purely hedonic pleasure that needs to be managed.

My personal bottom line: if you drink, try to be mindful about it. You’ll enjoy it more and suffer fewer consequences. Don’t just keep drinking because they’re serving it on the plane. I strongly urge my patients to limit alcohol to fewer than seven servings per week, and ideally no more than two on any given day, and I manage to do a pretty good job adhering to this rule myself.

We already know that it’s not good to consume excessive calories. In the form of carbohydrates, those extra calories can cause a multitude of problems, from NAFLD to insulin resistance to type 2 diabetes, as we saw in chapter 6. We know that elevated blood glucose, over a long enough period of time, amplifies the risk of all the Horsemen. But there is also evidence suggesting that repeated blood glucose spikes, and the accompanying rise(s) in insulin, may have negative consequences in and of themselves.

Now we have a tool to help us understand our own individual carbohydrate tolerance and how we respond to specific foods. This is called continuous glucose monitoring, or CGM, and it has become a very important part of my armamentarium in recent years.

From these studies, it seems quite clear that we want to lower average blood glucose and reduce the amount of variability from day to day and hour to hour. CGM is a tool that can help us achieve that. We use it in healthy people in order to help them stay healthy. That shouldn’t be controversial.

Also, everyone tends to be more insulin sensitive in the morning than in the evening, so it makes sense to front-load our carb consumption earlier in the day.

Also, sleep disruption or reduction dramatically impairs glucose homeostasis over time. From years of experience with my own CGM and that of my patients, it still amazes me how much even one night of horrible sleep cripples our ability to dispose of glucose the next day.

discovered another rule of nutrition, which is that timing is important: If you scarf a large baked potato before working out, it will leave much less of a footprint on your daily glucose profile than if you eat it right before bedtime.

Lessons from Continuous Glucose Monitoring In the years that I have used CGM, I have gleaned the following insights—some of which may seem obvious, but the power of confirmation cannot be ignored: Not all carbs are created equal. The more refined the carb (think dinner roll, potato chips), the faster and higher the glucose spike. Less processed carbohydrates and those with more fiber, on the other hand, blunt the glucose impact. I try to eat more than fifty grams of fiber per day. Rice and oatmeal are surprisingly glycemic (meaning they cause a sharp rise in glucose levels), despite not being particularly refined; more surprising is that brown rice is only slightly less glycemic than long-grain white rice. Fructose does not get measured by CGM, but because fructose is almost always consumed in combination with glucose, fructose-heavy foods will still likely cause blood-glucose spikes. Timing, duration, and intensity of exercise matter a lot. In general, aerobic exercise seems most efficacious at removing glucose from circulation, while high-intensity exercise and strength training tend to increase glucose transiently, because the liver is sending more glucose into the circulation to fuel the muscles. Don’t be alarmed by glucose spikes when you are exercising. A good versus bad night of sleep makes a world of difference in terms of glucose control. All things equal, it appears that sleeping just five to six hours (versus eight hours) accounts for about a 10 to 20 mg/dL (that’s a lot!) jump in peak glucose response, and about 5 to 10 mg/dL in overall levels. Stress, presumably, via cortisol and other stress hormones, has a surprising impact on blood glucose, even while one is fasting or restricting carbohydrates. It’s difficult to quantify, but the effect is most visible during sleep or periods long after meals. Nonstarchy veggies such as spinach or broccoli have virtually no impact on blood sugar. Have at them. Foods high in protein and fat (e.g., eggs, beef short ribs) have virtually no effect on blood sugar (assuming the short ribs are not coated in sweet sauce), but large amounts of lean protein (e.g., chicken breast) will elevate glucose slightly. Protein shakes, especially if low in fat, have a more pronounced effect (particularly if they contain sugar, obviously). Stacking the above insights—in both directions, positive or negative—is very powerful. So if you’re stressed out, sleeping poorly, and unable to make time to exercise, be as careful as possible with what you eat. Perhaps the most important insight of them all? Simply tracking my glucose has a positive impact on my eating behavior. I’ve come to appreciate the fact that CGM creates its own Hawthorne effect, a phenomenon where study subjects change their behavior because they are being observed. It makes me think twice when I see the bag of chocolate-covered raisins in the pantry, or anything else that might raise my blood glucose levels.

Protein and amino acids are the essential building blocks of life. Without them, we simply cannot build or maintain the lean muscle mass that we need. As we saw in chapter 11, this is absolutely critical to our strategy, because the older we get, the more easily we lose muscle, and the more difficult it becomes to rebuild it.

Unlike carbs and fat, protein is not a primary source of energy. We do not rely on it in order to make ATP,[*8] nor do we store it the way we store fat (in fat cells) or glucose (as glycogen). If you consume more protein than you can synthesize into lean mass, you will simply excrete the excess in your urine as urea. Protein is all about structure. The twenty amino acids that make up proteins are the building blocks for our muscles, our enzymes, and many of the most important hormones in our body. They go into everything from growing and maintaining our hair, skin, and nails to helping form the antibodies in our immune system. On top of this, we must obtain nine of the twenty amino acids that we require from our diet, because we can’t synthesize them.

How much protein do we actually need? It varies from person to person. In my patients I typically set 1.6 g/kg/day as the minimum, which is twice the RDA. The ideal amount can vary from person to person, but the data suggest that for active people with normal kidney function, one gram per pound of body weight per day (or 2.2 g/kg/day) is a good place to start—nearly triple the minimal recommendation.

The literature suggests that the ideal way to achieve this is by consuming four servings of protein per day, each at ~0.25 g/lb of body weight. A six-ounce serving of chicken, fish, or meat will provide about 40 to 45 grams (at about 7 grams of actual protein per ounce of meat), so our hypothetical 180-pound person should eat four such servings a day.

How much protein you need depends on your sex, body weight and lean body mass, activity level, and other factors, including age. There is some evidence that older people might require more protein because of the anabolic resistance that develops with age—that is, their greater difficulty in gaining muscle.

For me and my patients, this works out to four servings, as described, with at least one of them being a whey protein shake. (It’s very difficult for me to consume four actual meals. Typically, I will consume a protein shake, a high-protein snack, and two protein meals.)

One study found that giving elderly people supplements containing essential amino acids (that is, mimicking some effects of increasing dietary protein) lowered their levels of liver fat and circulating triglycerides. Another study in men with type 2 diabetes found that doubling their protein intake from 15 to 30 percent of total calories, while cutting carbohydrates by half, improved their insulin sensitivity and glucose control. Eating protein also helps us feel satiated, inhibiting the release of the hunger-inducing hormone ghrelin, so we eat fewer calories overall.

The key thing to remember—and somehow this is almost always overlooked—is that virtually no food belongs to just one group of fats. Olive oil and safflower oil might be as close as you can get to a pure monounsaturated fat, while palm and coconut oil might be as close as you can get to a pure saturated fat, but all foods that contain fats typically contain all three categories of fat: PUFA, MUFA, and SFA. Even a ribeye steak contains a lot of monounsaturated fats.

Putting all these changes into practice typically means eating more olive oil and avocados and nuts, cutting back on (but not necessarily eliminating) things like butter and lard, and reducing the omega-6-rich corn, soybean, and sunflower oils—while also looking for ways to increase high-omega-3 marine PUFAs from sources such as salmon and anchovies.

Protein is actually the most important macronutrient, the one macro that should not be compromised. Remember, most people will be overnourished—but also undermuscled. It is counterproductive for them to limit calories at the expense of protein and hence muscle mass.

(If there is one type of food that I would eliminate from everyone’s diet if I could, it would be fructose-sweetened drinks, including both sodas and fruit juices, which deliver too much fructose, too quickly, to a gut and liver that much prefer to process fructose slowly. Just eat fruit and let nature provide the right amount of fiber and water.)

In the end, the best nutrition plan is the one that we can sustain. How you manipulate the three levers of diet—calorie restriction, dietary restriction, and time restriction—is up to you.

How to Learn to Love Sleep, the Best Medicine for Your Brain Each night, when I go to sleep, I die. And the next morning, when I wake up, I am reborn. —Mahatma Gandhi

We now know that chronic sleep debt is a far more insidious killer than the acute sleep deprivation that results in falling asleep at stop signs. Many studies have found powerful associations between insufficient sleep (less than seven hours a night, on average) and adverse health outcomes ranging from increased susceptibility to the common cold to dying of a heart attack. Poor sleep dramatically increases one’s propensity for metabolic dysfunction, up to and including type 2 diabetes, and it can wreak havoc with the body’s hormonal balance.

A 2014 observational study found that young athletes who slept less than six hours per night were more than two and a half times more likely to experience an injury than their peers who slept eight hours or more.

Good sleep is like a performance-enhancing drug.

Even in the short term, sleep deprivation can cause profound insulin resistance. Sleep researcher Eve van Cauter of the University of Chicago subjected healthy young people to severely restricted sleep, just 4.5 hours a night, and found that after four days they had the elevated insulin levels of obese middle-aged diabetics and, worse yet, approximately a 50 percent reduction in their capacity for glucose disposal. This turns out to be one of the most consistent findings in all of sleep research. No fewer than nine different studies have found that sleep deprivation increases insulin resistance by up to a third.

increased insulin resistance and more of the diseases that accompany it, from NASH and type 2 diabetes to heart disease. If your sleep is chronically compromised, then your metabolism might be too.

high overnight glucose on CGM is almost always a sign of excessive cortisol, sometimes exacerbated by late-night eating and drinking. If it persists, this elevated blood glucose can lead to type 2 diabetes.

Translation: good sleep may help mitigate some of the genetic risk of heart disease faced by people like me. All of the above has convinced me to make sleep a top priority in my own life, and to pay attention to my patients’ sleep habits.

Perhaps most intriguing, REM sleep helps us maintain our emotional awareness. When we are deprived of REM, studies have found, we have a more difficult time reading others’ facial expressions. REM-deprived study subjects interpreted even friendly or neutral expressions as menacing. This is not trivial: our ability to function as social animals[*3] depends on our ability to understand and navigate the feelings of others. In short, REM sleep seems to protect our emotional equilibrium, while helping us process memories and information.

Like so much else in biology, this has a possible basis in evolution: if all members of a clan or a tribe adhered to the exact same sleep schedule, the entire group would be vulnerable to predators and enemies for several hours every night. Obviously not ideal. But if their sleep schedules were staggered, with some individuals going to bed early while others were more inclined to stay up late and tend the fire, the group as a whole would be much less vulnerable. This may also explain why teenagers want to go to bed late and then sleep in: Our chronotype appears to undergo a temporary shift in adolescence toward late sleeping and later rising. School start times, unfortunately for both teens and for those of us who are parents, remain stubbornly fixed at very early hours—but there is a growing nationwide movement to push school times later, to better suit adolescent sleep schedules.

I am increasingly persuaded that our 24-7 addiction to screens and social media is perhaps our most destructive habit, not only to our ability to sleep but to our mental health in general. So I banish those from my evenings (or at least, I try to). Turn off the computer and put away your phone at least an hour before bedtime. Do NOT bring your laptop or phone into bed with you.

Coffee is not a solution to the problem of poor sleep, especially if consumed to excess or (especially) at the wrong time. Most people think of caffeine as a stimulant that somehow gives us energy, but actually it functions more as a sleep blocker. It works by inhibiting the receptor for a chemical called adenosine, which normally helps us go to sleep every night. Over the course of the day, adenosine builds up in our brain, creating what scientists call “sleep pressure,” or the drive to sleep. We may be tired and needing sleep, but if we ingest caffeine it effectively takes the phone off the hook, so our brain never gets the message.

Another way to help cultivate sleep pressure is via exercise, particularly sustained endurance exercise (e.g., zone 2), ideally not within two or three hours of bedtime. My patients often find that a thirty-minute zone 2 session can do wonders for their ability to fall asleep. Even better is exercise that entails some exposure to sunlight (i.e., outdoors). While blue light late in the evening can interfere with sleep, a half-hour dose of strong daylight, during the day, helps keep our circadian cycle on track, setting us up for a good night of sleep.

The overarching point here is that a good night of sleep may depend in part on a good day of wakefulness: one that includes exercise, some outdoor time, sensible eating (no late-night snacking), minimal to no alcohol, proper management of stress, and knowing where to set boundaries around work and other life stressors.

Don’t drink any alcohol, period—and if you absolutely, positively must, limit yourself to one drink before about 6 p.m. Alcohol probably impairs sleep quality more than any other factor we can control. Don’t confuse the drowsiness it produces with quality sleep.

Fix your wake-up time—and don’t deviate from it, even on weekends. If you need flexibility, you can vary your bedtime, but make it a priority to budget for at least eight hours in bed each night.

Every man is a bridge, spanning the legacy he inherited and the legacy he passes on. —Terrence Real

“Religion is for people who are afraid of Hell. Spirituality is for people who have been there.”

This is why I’ve come to believe that emotional health may represent the most important component of healthspan. Nothing else about longevity is really worth much without some degree of happiness, fulfillment, and connection to others. And misery and unhappiness can also destroy your physical health, just as surely as cancer, heart disease, neurodegenerative disease, and orthopedic injury.

It took me a while to recognize this, but feeling connected and having healthy relationships with others, and with oneself, is as imperative as maintaining efficient glucose metabolism or an optimal lipoprotein profile. It is just as important to get your emotional house in order as it is to have a colonoscopy or an Lp(a) test, if not more so. It’s just a lot more complicated.

Emotional health has more to do with the way we regulate our emotions and manage our interpersonal relationships.

What makes dealing with emotional health harder than physical health, I suspect, is that we are often less able to recognize the need to make changes. Few people who are overweight and out of shape fail to realize they need to make a change.

At the Bridge, I learned that children don’t respond to a parent’s anger in a logical way. If they see me screaming at a driver who just cut me off, they internalize that rage as though it were directed to them. Second, trauma is generational, although not necessarily linear. Children of alcoholics are not inevitably destined to become alcoholics themselves, but one way or another, trauma finds its way down the line.

As Terry had written: “Family pathology rolls from generation to generation like a fire in the woods taking down everything in its path until one person, in one generation, has the courage to turn and face the flames. That person brings peace to his ancestors and spares the children that follow.” I wanted to be that person.

One skill I worked on that is a bit more complicated is called “reframing.” Reframing is basically the ability to look at a given situation from someone else’s point of view—literally reframing it.

need to be great,” he said, “in order to feel like I’m not worthless.”

Who cares how well you perform if you’re so utterly miserable?

“When nothing seems to help, I go back and look at a stonecutter hammering away at his rock perhaps a hundred times without as much as a crack showing in it. Yet at the hundred-and-first blow it will split in two, and I know it was not the last blow that did it, but all that had gone before.”

True recovery requires probing the depths of what shaped you, how you adapted to it, and how those adaptations are now serving you (or not, as in my case). This also takes time, as I found out the hard way; the biggest mistake of all is to believe that you’re “cured,” by a few months on a drug or a handful of therapy sessions, when in fact you’re not even halfway there.

The practice of DBT is predicated on learning to execute concrete skills, repetitively, under stress, that aim to break the chain reaction of negative stimulus → negative emotion → negative thought → negative action.

Another way in which mindfulness helps is by reminding us that when we are suffering, it is rarely because of some direct cause, like a rock that is crushing our leg at this very moment. Much more often, it is because we are thinking about some painful event that occurred in the past or worrying about something bad that may occur in the future. This, too, was an enormous revelation to me. Simply put, I experience less pain because I am able to recognize when the source of that pain is inside my own head. This was not an original insight, but it was nevertheless profound. I was about 2,500 years behind the Buddha, who said that “your worst enemy cannot harm you as much as your own unguarded thoughts.” Seneca improved on that in the first century AD, observing that “we suffer more often in imagination than in reality.” And later, in the sixteenth century, Shakespeare’s Hamlet noted, “There is nothing either good or bad, but thinking makes it so.”

This small lesson, which I have implemented countless times since, taught me something very important: changing the behavior can change the mood. You do not need to wait for your mood to improve to make a behavior change. This is also why cognitive therapies alone sometimes come up short; simply thinking about problems might not help if our thinking itself is disordered.

If you take nothing else from my story, take this: If I can change, you can change. All of this has to begin with the simple belief that real change is possible. That’s the most important step. I believed I was the most horrible, incorrigible, miserable son of a bitch that was ever shat into civilization. For as long as I could remember, I believed that I was defective and that my flaws were hard-wired. Unchangeable. Only when I at least entertained the notion that maybe I was not actually a monster was I able to start chipping away at the narrative that had nearly destroyed my life and everyone in my wake. This is the key step. You have to believe you can change—and that you deserve better.

As I settled into the next phase of my recovery, I began to notice something I had never experienced before: I found more joy in being than in doing. For the first time in my life, I felt that I could be a good father. I could be a good husband. I could be a good person. After all, this is the whole point of living. And the whole point of outliving. There’s a quote from Paulo Coelho that I think about often: “Maybe the journey isn’t so much about becoming anything,” he writes. “Maybe it’s about unbecoming everything that isn’t really you, so you can be who you were meant to be in the first place.”

longevity is meaningless if your life sucks. Or if your relationships suck. None of it matters if your wife hates you. None of it matters if you are a shitty father, or if you are consumed by anger or addiction. Your résumé doesn’t really matter, either, when it comes time for your eulogy.

“I think people get old when they stop thinking about the future,” Ric told me. “If you want to find someone’s true age, listen to them. If they talk about the past and they talk about all the things that happened that they did, they’ve gotten old. If they think about their dreams, their aspirations, what they’re still looking forward to—they’re young.” Here’s to staying young, even as we grow older.