Outlive: The Science and Art of Longevity: The Million-Copy Bestseller

by Peter Attia

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.

Death rates from cancer,3 on the other hand, have hardly budged in the more than fifty years since the War on Cancer was declared, despite hundreds of billions of dollars’ worth of public and private spending on research.

None of our treatments for late-stage lung cancer has reduced mortality by nearly as much as the worldwide reduction in smoking that has occurred over the last two decades, thanks in part to widespread smoking bans. This simple preventive measure (not smoking) has saved more lives than any late-stage intervention that medicine has devised. Yet mainstream medicine still insists on waiting until the point of diagnosis before we intervene.

Hippocrates’s major contribution was the insight that diseases are caused by nature and not by actions of the gods, as had previously been believed.

A treatment that works for one patient may prove useless in the other, either because her immune system is reacting differently or because her infection is viral rather than bacterial. Even now, it remains extremely difficult to tell the difference, resulting in millions of useless antibiotic prescriptions.

To achieve our objectives, we first need to have a strategy: an overall approach, a conceptual scaffolding or mental model that is informed by science, is tailored to our goals, and gives us options.

The centenarians not only live longer but live longer in a healthier state, meaning many of them get to enjoy one, or two, or even three Bonus Decades. They are often healthier at ninety than the average person in their sixties. And when they do decline, their decline is typically brief.

the gene (or genes) responsible for male pattern baldness. When we are young, our hair is full and glorious, helping us attract mates. But natural selection does not really care whether a man in his fifties (or a woman, for that matter) has a full head of hair.

Normally, a healthy liver is a deep, dark purple color, with a gorgeous silky-smooth texture. Hannibal Lecter was not too far off: it really does look as if it might be delicious with some fava beans and a nice Chianti.

Fat also begins to infiltrate your abdomen, accumulating in between your organs. Where subcutaneous fat is thought to be relatively harmless, this “visceral fat” is anything but.

This is why I insist my patients undergo a DEXA scan annually—and I am far more interested in their visceral fat than

Cortisol is especially potent, with a double-edged effect of depleting subcutaneous fat (which is generally beneficial) and replacing it with more harmful visceral fat. This is one reason why stress levels and sleep, both of which affect cortisol release, are pertinent to metabolism.

What is the most common “presentation” (or symptom) of heart disease? It wasn’t chest pain, left arm pain, or shortness of breath, the most common answers; it was sudden death.

three of the major prerequisites for heart disease: significant lipoprotein burden or apoB, LDL oxidation or modification (leading to the plaques that my calcium scan revealed), and a high level of background inflammation.

our best hope likely lies in figuring out better ways to attack cancer on all three of these fronts: prevention, more targeted and effective treatments, and comprehensive and accurate early detection.

Breast cancer kills only when it becomes metastatic. Prostate cancer kills only when it becomes metastatic. You could live without either of those organs. So when you hear the sad story of someone dying from breast or prostate cancer, or even pancreatic or colon cancer, they died because the cancer spread to other, more critical organs such as the brain, the lungs, the liver, and bones. When cancer reaches those places, survival rates drop precipitously.

one way to locate potential tumors is by injecting the patient with radioactively labeled glucose and then doing a PET scan to see where most of the glucose is migrating.

Three of these drugs, known as PI3K inhibitors, have been FDA approved for certain relapsed leukemias and lymphomas, and a fourth was approved in late 2019 for breast cancer.

She devoured everything she could read on the impact of nutrition on cancer, and she had concluded that a diet that reduced insulin and IGF-1 would aid in her treatment. So she worked out a regimen that consisted primarily of leafy vegetables, olive oil, avocados, nuts, and modest amounts of protein, mostly from fish, eggs, and poultry. The diet was just as notable for what it did not contain: added sugar and refined carbohydrates. All along, she underwent frequent blood tests to make sure her insulin and IGF-1 levels stayed low, which they did.

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.

It took many more years and several iterations, but Rosenberg and his team23 adapted a technique that had been developed in Israel that involved taking T cells from a patient’s blood, then using genetic engineering to add antigen receptors that were specifically targeted to the patient’s tumors. Now the T cells were programmed to attack the patient’s cancer. Known as chimeric antigen receptor T cells (or CAR-T), these modified T cells could be multiplied in the lab and then infused back into the patient. In 2010, Rosenberg and his team reported their first success with a CAR-T treatment, in a patient with advanced follicular lymphoma who had undergone multiple rounds of conventional treatments, including chemotherapy, as well as a different kind of immunotherapy, all without success. Other groups pursued the technique as well, and finally, in 2017, the first two CAR-T-based treatments were approved by the FDA (making them the first cell and gene therapies ever approved by the FDA), one for adult lymphoma and another for acute lymphoblastic leukemia, the most common cancer in children. It had taken nearly fifty years, but Steve Rosenberg’s once-outlandish theory had finally yielded a breakthrough.

About a third of cancers can be treated with immunotherapy, and of those patients, just one-quarter will actually benefit (i.e., survive). That means that only 8 percent of potential cancer deaths could be prevented by immunotherapy,

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.

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

regular exercisers live as much as a decade longer3 than sedentary people.

peak aerobic cardiorespiratory fitness, measured in terms of VO2 max, is perhaps the single most powerful marker7 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.

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

Someone in the bottom quartile of VO2 max10 for their age group (i.e., the least fit 25 percent) is nearly four times likelier to die than someone in the top quartile—and five times likelier to die than a person with elite-level (top 2.3 percent) VO2 max.

But both physical activity levels and muscle mass decline steeply after about age sixty-five, and then even more steeply after about seventy-five. It’s as if people just fall off a cliff sometime in their mid-seventies.

Our mitochondria can convert both glucose and fatty acids to energy—but while glucose can be metabolized in multiple different ways, fatty acids can be converted to energy only in the mitochondria.

zone 2 training is for professional cyclists, however, San Millán believes that it’s even more important for nonathletes, for two reasons. First, it builds a base of endurance for anything else you do in life, whether that is riding your bike in a one-hundred-mile century ride or playing with your kids or grandkids.

supplementing our zone 2 work with one or two VO2 max workouts per week.

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.fn4 Group comparisons for VO2 max are Low (bottom 25%), Below Average (26th to 50th percentile), Above Average (51st to 75th percentile), High (75th to 97.6th percentile), and Elite (top 2.3%). Source: Mandsager et al. (2018). You want to make sure that you get as close to fully recovered as possible before beginning the next set. If you fail to recover sufficiently between sets, you will not be able to reach your peak effort in the working sets and you’ll consequently miss the desired adaptation. Also, be sure to give yourself enough time to warm up and then cool down from this intense effort.

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.

You bend at the hips—not the spine—to harness your body’s largest muscles, the gluteus maximus and the hamstrings.

stability is the subconscious ability to harness, decelerate, or stop force.

The goal is to be strong, fluid, flexible, and agile as you move through your world.

DNS. Short for dynamic neuromuscular stabilization, DNS sounds complicated, but it is based on the simplest, most natural movements we make: the way we moved when we were babies.

Hip-Hinging 101: How to Do a Step-Up

Looking back, I now realize that I was too far on the left on the Dunning-Kruger curve, caricatured below in figure 14—my maximal confidence and relatively minimal knowledge having propelled me quite close to the summit of “Mount Stupid.”

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 need to find ways to get them to consume fewer calories while also increasing their protein intake, and to pair this with proper exercise.

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.

we are unruly, disobedient, messy, forgetful, confounding, hungry, and complicated creatures.

you will need to apply at least one of these methods of caloric reduction: deliberately tracking (and reducing) what you eat; cutting out certain foods; and/or giving yourself less time in which to eat. That’s it.

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 y...

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.