When we are born, we aren't given an owner's manual. But now we have the book, "Outlive: The Science and Art of Longevity" by Peter Attia, MD. It provides direction for how we can live a long and healthy life. But it also shares a prescription for the things we need to do if we want to live longer despite the diseases that are out to get us, including cancer, heart disease, and type 2 diabetesAttia is well known for his medical advice on his podcast and in other venues. This book cautions us about what he calls the "four horsemen" of diseases that are likely to kill us: heart disease, cancer, neurodegenerative disease, or type 2 diabetes and related metabolic dysfunction. Despite limited progress in holding some of them back, Attia says modern medicine is still not very helpful until a disease is diagnosed before help is provided. "Someone who drops dead of a heart attack did not just get sick an hour earlier," he writes. "The disease was working inside them, silently and invisibly, for decades. Their internal defense mechanisms weakened as they grew older, and disease gained the upper hand. "Among the key takeaways from the book:• Current medicine relies on two tactics: procedures (e.g., surgery) and medications. But he suggests that future medicine should focus on five domains: exercise, nutrition, sleep, emotional health, and exogenous molecules, meaning drugs, hormones, or supplements.• 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. Similarly, one-quarter of the general population will have been diagnosed with clinically apparent cardiovascular disease by age seventy-five; among centenarians, that prevalence is reached only at age ninety-two.• When centenarians die, they have generally (though not always) been sick or disabled for a much shorter period than people who died two or three decades earlier.• 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.• Doctors should focus on metabolical obesity 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)• If you meet three or more of these criteria, you have the metabolic syndrome—along with as many as 120 million other Americans, according to a 2020 article in JAMA. About 90 percent of the US population ticks at least one of these boxes.• Metabolism is how we take nutrients and break them down for use in the body. Those nutrients are processed and sent to their proper destinations in someone who is metabolically healthy. But when someone is metabolically unhealthy, many calories they consume end up where they are not needed, at best—or outright harmful, at worst.• Fat also begins to infiltrate your abdomen, accumulating in between your organs.• Patients with diabetes have a much greater risk of cardiovascular disease, cancer, Alzheimer's disease, and other dementias; one could argue that diabetes with related metabolic dysfunction is one thing that all these conditions have in common. "This is why I place such emphasis on metabolic health and why I have long been concerned about the epidemic of metabolic disease not only in the United States but worldwide."• Humans have a unique capacity for turning calories from fructose into fat. Lots of people like to demonize fructose, especially in the form of high-fructose corn syrup, without really understanding why it's supposed to be so harmful. The story is complicated but fascinating. The critical factor here is that fructose is metabolized differently from other sugars. When we metabolize fructose, along with certain different types of foods, it produces large amounts of uric acid, best known as a cause of gout but also associated with elevated blood pressure.• Cholesterol is essential to life. It is required to produce some of the most critical structures in the body, including cell membranes; hormones such as testosterone, progesterone, estrogen, and cortisol; and bile acids, which are necessary for digesting food.• The humble egg, in particular, was singled out in a 1968 proclamation by the American Heart Association, accused of causing heart disease because of its high cholesterol content. It has remained in nutritional purgatory for decades, even after reams of research papers showing that dietary cholesterol (and particularly egg consumption) may not have much to do with heart disease at all. Eating lots of saturated fat can increase levels of atherosclerosis-causing lipoproteins in blood, 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.• 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. The difference is that we understand the genesis and progression of heart disease fairly well, and we have some effective tools with which to prevent and treat it. As a result, mortality rates from cardiovascular disease and cerebrovascular disease have dropped by two-thirds since the middle of the twentieth century. But cancer still kills Americans at almost exactly the same rate as it did fifty years ago. We have made some progress against a few specific cancers, notably leukemia (especially childhood leukemia, as I noted earlier). For adults with leukemia, ten-year survival rates nearly doubled between 1975 and 2000, leaping from 23 percent to 44 percent. Survival rates for Hodgkin's and non-Hodgkin's lymphomas have increased as well, especially the former. Yet these represent relatively small victories in a "war" that has not gone particularly well.• The problem we face is that once cancer is established, we lack highly effective treatments for it. Our toolbox is limited. Many (though not all) solid tumors can be removed surgically, a tactic that dates back to ancient Egypt. Combining surgery and radiation therapy is pretty effective against most local, solid-tumor cancers. But while we've gotten fairly good at this approach, we have essentially maxed out our ability to treat cancers this way. We are not getting any more juice from the squeeze.• 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.• Five decades into the war on cancer, it seems clear that no single "cure" is likely to be forthcoming. Rather, 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.• But what causes cancer to spread? We don't really know, and we are unlikely to find out anytime soon because only about 5 to 8 percent of US cancer research funding goes to the study of metastasis. Our ability to detect cancer metastasis is also very poor, although I do believe we are on the verge of some key breakthroughs in cancer screening,• Right now, this usually means chemotherapy. Contrary to popular belief, killing cancer cells is actually pretty easy. Traditional chemotherapy occupies a fuzzy region between poison and medicine.• 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.• If the first rule of cancer is "Don't get cancer," the second rule is "Catch it as soon as possible."• Alzheimer's disease is perhaps the most difficult, most intractable of the Horsemen diseases. We have a much more limited understanding of how and why it begins, and how to slow or prevent it, than we do with atherosclerosis.• While female Alzheimer's patients outnumber men by two to one, the reverse holds true for Lewy body dementia and Parkinson's, both of which are twice as prevalent in men. Yet Parkinson's also appears to progress more rapidly in women than in men, for reasons that are not clear.Finally, the author suggests how medicine needs to change it focus:• The first is exercise, which I consider to be by far the most potent domain in terms of its impact on both lifespan and health span.• Next is diet or nutrition—or as I prefer to call it, nutritional biochemistry.• The third domain is sleep, which has gone underappreciated by Medicine 2.0 until relatively recently.• The fourth domain encompasses a set of tools and techniques to manage and improve emotional health.• Our fifth and final domain consists of the various drugs, supplements, and hormones that doctors learn about in medical school and beyond.