Outlive: The Science and Art of Longevity

“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.”

This passage highlights one key theme of Attia’s book: The Failures of Modern Medicine (Medicine 2.0). Despite decades of trying, modern medicine fails to stop most people from dying of the Four Horsemen (metabolic dysfunction, heart disease, cancer, and neurogenerative diseases). The reason is that modern medicine intervenes when these diseases have become entrenched in the human body. Attia argues that medicine and people alike need a mindset change: Rather than being reactive to these diseases, people need to focus on being proactive, preventing these diseases from taking hold in their bodies.

“Risk is not something to be avoided at all costs; rather, it’s something we need to understand, analyze, and work with.”

Attia argues that one of The Failures of Modern Medicine (Medicine 2.0) is that it is too averse to risk. Part of why Medicine 2.0 does not account for risk is because it relies on clinical trials. Clinical trials focus on how risks associated with new treatments impact the study group as a whole rather than the different individuals that comprise the group. Clinical trials do not take into consideration nuances involved with risk. This reality often harms patients. As a result, Attia’s Medicine 3.0 accepts risk, in part because it focuses on patients as individuals. Attia is willing to dive deeper into risk because he focuses on individual patients and their unique symptoms, family history, genetics, etc.

“Nearly all the money flows to treatment rather than prevention—and when I say ‘prevention,’ I mean prevention of human suffering.”

The current American healthcare system business model is ill-equipped to handle Medicine 3.0, because health insurance companies currently do not reward patients for proactive treatment plans or doctors for helping patients prevent chronic disease. Instead, these companies fund the actual treatment of chronic diseases, which is the focus of Medicine 2.0. This results in human suffering. Attia argues that patients and medical professionals need to push the field (including health insurance companies) to start taking longevity seriously and rethink how we view treatment and chronic diseases. This passage reflects Attia’s interest in Proactive Versus Reactive Medicine.

“Without an understanding of the strategy and science that informs it, our tactics will not mean much, and you’ll forever ride the merry-go-round of fad diets and trendy workouts and miracle supplements.”

Attia focuses on a three-part approach for longevity: objectives, strategy, and tactics. To him, strategy represents the most important component. Evidence-based strategies allow us to slow the deterioration of our bodies, emotions, and mind because we think critically about the tactics that will work best for our individual circumstances. Rushing to implement tactics without research will prevent us from addressing these declines. Thus, we will continue to compromise rather than improve our healthspans. We might live longer but our quality of life will likely be poor without investing in strategy.

“The crucial distinction […] is that they [centenarians] tend to develop these diseases much later in life than the rest of us—if they develop them at all. We’re not talking about two or three or even five years later; we’re talking decades. According to research by Thomas Perls of Boston University and his colleagues, who run the New England Centenarian Study, one in five people in the general population will have received some type of cancer diagnosis by age seventy-two. Among centenarians, that one-in-five threshold is not reached until age one hundred, nearly three decades later.”

Research by Perls and others demonstrates that centenarians have genes that enable a phase shift, meaning their lifespan and healthspan trajectory has shifted several decades to the right of the average person. These genes result in centenarians being biologically younger than their peers for decades. Unfortunately, there is not one longevity gene—instead, there are likely many genes that help centenarians live longer and healthier lives. Attia thus advocates genetic screening to inform strategies for reaching longevity.

“‘There is a very low tolerance for side effects, by the public and by regulatory agencies, if you’re talking about treating a healthy person,’ says Kaeberlein. ‘The intent is to slow aging in people before they are sick, to keep them healthy longer, so in many ways it is the opposite of traditional biomedical approach, where normally we wait until people are sick and then we try to cure their diseases.’”

American biologist Matt Kaeberlein is conducting a large experiment on dogs, which are a good proxy for humans because they age in similar ways, are mammals, are large, and share similar environments. He is hoping to demonstrate that the benefits of rapamycin outweigh its risks. Here, Kaeberlein underscores the fundamental issue with Medicine 2.0: its inability to recognize the importance of slowing aging and delaying disease. Instead, treatment of disease once it already occurs within the body is the primary concern of Medicine 2.0. It is much more difficult to treat disease at this point, which shortens human lifespan and healthspan. Kaeberlein believes that we should be able to use rapamycin to help healthy people maintain high quality of life for longer, reflecting the debate about Proactive Versus Reactive Medicine.

“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 is not wanted or needed, like onto the bathroom floor, into the heating vents, or down the stairs.”

Throughout the book, Attia uses a number of different analogies to help explain complex biological processes. The use of a bathtub to illustrate what happens to excess fat in the body is one example. Like a bathtub with water, the body’s subcutaneous fat tissues can take in calories. However, like the bathtub, subcutaneous fat also reaches its capacity. When this capacity is reached, the excess energy, like the still-running water, needs a place to go. The energy moves to other places within the body (including muscles, liver, pancreas, etc.), like the water flows to the bathroom floor, downstairs, or heating vents, where it causes damage, since the energy/water does not belong in these places.

“If we want to reduce deaths from cardiovascular disease, we need to begin thinking about prevention in people in their forties and even thirties.”

Attia’s belief that we need to start prevention treatment for ASCVD when people are in their thirties and forties represents a radical departure from Medicine 2.0. Medicine 2.0 insists that this age bracket is too young for someone to begin focusing on cardiac disease prevention. However, research shows that many of the precursors to heart disease start developing when we are teenagers, especially apoB/LDL burden. Attia argues that the only way to stop heart disease is to remove these precursors. The best time to do it is when someone is young before they take hold and form heart disease. This passage reflects Attia’s interest in Proactive Versus Reactive Medicine.

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

Compared to the other three Horsemen diseases, cancer is one of the trickiest to prevent since mutations, smoking, and metabolic dysfunctions are key drivers. Attia notes that we can reduce risks associated with the last two drivers, but mutations are often out of our control. As such, he advocates for aggressive and early screening of cancer types. Medicine 2.0 balks at this strategy since many false positives are associated with many cancer screening tests. Attia, however, disagrees. He believes that we should use multiple screening tests as well as be strategic about who we are testing. Furthermore, Attia argues that costs associated with these tests (including financial and emotional) do not outweigh early cancer detection. We can treat cancer much more easily in its early stages compared to advanced stages. He hopes that better screening and more effective treatments will render cancer as an obsolete Horsemen, making it a manageable disease.

“The single most powerful item in our preventive tool kit is exercise, which has a two-pronged impact on Alzheimer’s disease risk: it helps maintain glucose homeostasis, and it improves the health of our vasculature.”

Medicine 2.0 only steps in when there is a dementia diagnosis and it is not able to reverse cognitive impairment. However, Attia argues that Medicine 3.0 offers a more hopeful path: By understanding the inner workings of the brain, we can develop strategies that help us maintain brain health, which will delay the onset of Alzheimer’s disease. To Attia, exercise is the most powerful tool in our toolkit. It improves our vascular and metabolic health, which improves brain health.

“This new environment we have created is potentially toxic with respect to what we eat (chronically, not acutely), how we move (or don’t move), how we sleep (or don’t sleep), and its overall effect on our emotional health (just spend a few hours on social media).”

One idea that Attia returns to throughout the book is that there is a mismatch between our evolutionary and modern environments. Our genes evolved in a particular environment (the grasslands of Africa) over millennia. Our modern environment is new (within the last few hundred years). While our environment has changed, many of our genes have not yet done so. As a result, genes and traits that were once adaptive (i.e., allowed humans to reproduce), are now considered “maladaptive.” As such, Attia argues that we need to work harder, including by getting our nutrition, emotional health, and exercise and sleep routine in order if we want to embrace The Importance of Living Better for Longer.

“More than any other tactical domain in this book, exercise has the greatest power to determine how you will live out the rest of your life.”

The hallmark of aging is physical decline, but Attia argues that this does not have to be our outcome. Instead, exercising has the power to extend both lifespan and healthspan. However, a person must maintain a high level of fitness throughout their life to prevent this physical decline.

“In every case, you need to be doing much more now, to armor yourself against the natural and precipitous decline in strength and aerobic capacity that you will undergo as you age.”

Attia shares his Centenarian Decathlon framework which encourages his patients to think about their physical aspirations in their later years of life. Central to this framework is the idea that we need to be doing more now to prepare for our natural physical decline due to age. For example, if his patient hopes to climb several flights of stairs in their eighties, then Attia argues they need to be able to sprint up those stairs today. Similarly, if a patient hopes to be able to lift their own suitcase into an airplane overhead storage bin later in life, then they need to be able to lift double or triple the weight of their suitcase now. While this might sound impossible, Attia notes that there are currently people in their eighties, nineties, and beyond who can do all these things. Exercise enables us to slow our strength and aerobic capacity declines.

“Studies suggest that your VO₂ max will decline by roughly 10 percent per decade—and up to 15 percent per decade after the age of fifty. So simply having average or even above-average VO₂ max now just won’t cut it.”

If a person has a VO₂ max number of 32 ml/kg/min at age 50, their VO₂ max number will drop to 21 ml/kg/min at age 80. This drop will drastically reduce a person’s physical capabilities, likely preventing them from doing the types of physical activities that they had hoped to do when they were in their eighties. Attia uses the results from this study to emphasize that he is having readers train for their Centenarian Decathlon. To him, having a VO₂ max number that is average or above-average now will not enable people to do the activities they hope to do in their later years. Instead, readers must be willing to train so that their VO₂ max number is in the elite category for their age and sex. Only by doing so will they maintain the level of physical capability that they hope to later in life.

“I think of strength training as a form of retirement savings.”

Comparing strength training to a form of “retirement savings” is another analogy by Attia that reflects on the theme of Proactive Versus Reactive Medicine. Like saving for retirement, Attia encourages readers to build their muscle strength, mass, and bone density (wealth) gradually over many years. Strength training, like investing in retirement savings, also compounds through time: Building up our reserves early means that we will have a large reserve later in life.

“People like Barry help us to rewrite that narrative of decline that trapped my friend’s mom, Sophie, and so many other people. Exercise has the power to change us profoundly, even if we’re starting from zero, as Barry was. It gives us the ability to pick ourselves up off the ground—literally and figuratively—and become stronger and more capable. It’s not about slowing the decline, it’s about getting better, and better, and better.”

Barry was an octogenarian at the time that he decided to get into physical shape. He spent the majority of his life focusing on his job, neglecting his health. When he retired, Barry realized that he was in terrible shape and constant pain. He was looking at a Marginal Decade rather than a Bonus Decade (See: Index of Terms). By working with one of Attia’s friends, Barry worked on his stability training, including learning a sequence of movements that allowed him to get up from a seated position without using his hands (which is a big deal for someone in their eighties). His physical health improved, and he no longer had chronic pain. Attia uses Barry’s story to show that exercise truly is the most powerful longevity drug.

“Diet and nutrition are so poorly understood by science, so emotionally loaded, and so muddled by lousy information and lazy thinking that it is impossible to speak about them in nuanced terms at a party or, say, on social media. Yet most people these days are conditioned to want bullet-point ‘listicles,’ bumper-sticker slogans, and other forms of superficial analysis.”

Attia takes issue with the notion that nutrition, like exercise, is a magic bullet for extending lifespan and healthspan. The reason for his belief is that we know so little about nutrition. For this reason, he takes issue with fad diets. Each fad diet has supporters that defend their way of eating, even when it conflicts with science. Attia admits that he used to be one of these zealous warriors for low-carb and ketogenic diets. He now firmly believes that there is no one diet that works best for everyone.

“To me, perhaps the most vexing issue with diet and nutrition studies is the degree of variation between individuals that is found but often obscured.”

By examining the flaws associated with the two types of nutrition research studies (epidemiology and clinical trials), Attia underscores his main argument in Chapter 14: We know very little about nutrition research. Perhaps most surprising, however, is how much individualism matters to nutritional biochemistry, yet nutrition research ignores individual results. Studies on the Mediterranean diet represent one example. Studies report average findings which obscure individual results: Some individuals lost a lot of weight on the diet, whereas others did not. Attia believes that people need to find the best eating plan for themselves rather than following fad diets and nutrition research.

“There’s no minimum requirement for carbohydrates or fats (in practical terms), but if you shortchange your protein, you will most certainly pay the price, particularly as you age.”

According to the US recommended dietary allowance (RDA), protein consumption is 0.8 g/kg of body weight. Numerous studies have shown that this amount is far too little, especially for elderly people. Consuming the daily recommendation caused faster muscle loss, which is the opposite of what we want to happen as we age. Attia advocates for far greater protein consumption (around 1.6 g/kg/day as his minimum). Protein consumption is another area he believes illustrates The Failures of Modern Medicine (Medicine 2.0). Despite studies showing that consuming too little protein has adverse health effects, the RDA has not changed. Medicine 2.0 is not nimble, making it unable to adapt to new research and individual needs.

“In the end, the best nutrition plan is the one that we can sustain.”

Here, Attia reinforces his belief that fad diets should be discarded. Based on research and his own observations, there is no one diet that meets every person’s needs. Instead, he argues that people need to manipulate caloric restriction, dietary restriction, and time restriction (three levers of diet) in a way that helps them improve or maintain weight, blood glucose, insulin, and lipid levels, muscle mass and strengthen, and bone density.

“We now know that sleep is as fundamental to our health as stability is fundamental to our strengthen.”

In Chapter 16, Attia addresses a number of myths about sleep, including that sleep is unimportant. Sleep is often deprioritized in our modern environment. Research suggests that chronic sleep disruption leads to severe health issues. Good quality and quantity sleep is essential to metabolic, heart, and brain health, helping to reduce metabolic dysfunction and heart disease and the risks of neurogenerative disease.

“Coffee is not a solution to the problem of poor sleep, especially if consumed to excess or (especially) at the wrong time.”

Another myth that Attia discusses is that coffee gives us energy. Instead, coffee functions as a sleep blocker. Caffeine’s half-life in the body is up to six hours. For this reason, drinking caffeine later in the day often prevents people from falling asleep (unless they have caffeine tolerance). Attia suggests that people who metabolize coffee slowly should stop drinking it by lunch time.

“Emotional health and physical health are closely intertwined, in ways that mainstream medicine, Medicine 2.0, is still only beginning to grasp.”

While Medicine 2.0 pays attention to physical health, it does not pay as much attention to emotional health. Emotional health is much harder to manage, maintain, and restore, in part because people do not always recognize when it has fallen out of equilibrium. By discussing his own emotional health journey, Attia shows that we can shift our mindset to address emotional health disorders. Failure to have good emotional and physical health will negatively impact our healthspan. We might be physically fit in our later years, but if we can’t enjoy them, it will not be much of a victory. Both physical and emotional health are thus important when addressing The Importance of Living Better for Longer.