A groundbreaking manifesto on living better and longer that challenges the conventional medical thinking on aging and reveals a new approach to preventing chronic disease and extending long-term health, from a visionary physician and leading longevity expert

Wouldn’t you like to live longer? And better? In this operating manual for longevity, Dr. Peter Attia draws on the latest science to deliver innovative nutritional interventions, techniques for optimizing exercise and sleep, and tools for addressing emotional and mental health.

For all its successes, mainstream medicine has failed to make much progress against the diseases of aging that kill most people: heart disease, cancer, Alzheimer’s disease, and type 2 diabetes. Too often, it intervenes with treatments too late to help, prolonging lifespan at the expense of healthspan, or quality of life. Dr. Attia believes we must replace this outdated framework with a personalized, proactive strategy for longevity, one where we take action now, rather than waiting.

Review

People familiar with Peter Attia will realise he is not a life extensionist. By longevity (or what he is rebranding as outliving) he means in the sense of living longer and living better - as in being in the top 10% of lifespans, not living longer than anyone who has lived before. And to do that, he is focussed on preventative medicine, particularly around exercise, diet, sleep and mental health.

Given that there are no proven rejuvenatation treatments available as of 2023, this is a good place to start - if you can live 10 years longer than the average in your country, that's 10 more years of medical breakthroughs that could then develop true longevity treatments to slow and reverse ageing.

Highlights

Given the length of this tome on longevity, it was always going to be a struggle to keep to the usual 100 highlights, so here are 188 key points from Outlive by Peter Attia.

• The word longevity has been hopelessly tainted by a centuries-long parade of quacks and charlatans.
• Since 1900, slow death has supplanted fast death.
• Death rates from cancer have hardly budged in the more than fifty years since the War on Cancer was declared.
• We should be proactive instead of reactive in our approach.
• We want to delay or prevent these conditions so that we can live longer without disease, rather than lingering with disease.
• In today’s unhealthy society, “normal” or “average” is not the same as “optimal.”
• With enough time and effort, you can potentially extend your lifespan by a decade
• Medicine 1.0 was based on direct observation and abetted more or less by pure guesswork.
• Medicine 2.0 arrived in the mid-nineteenth century with the advent of the germ theory of disease.
• If you subtract out deaths from the eight top infectious diseases, overall mortality rates declined relatively little over the course of the twentieth century.
• Atherosclerosis begins many decades before the person has a coronary “event” that could result in their death.
• Medicine 3.0 places a far greater emphasis on prevention than treatment.
• Medicine 3.0 considers the patient as a unique individual.
• Medicine 3.0's starting point is the honest assessment, and acceptance, of risk—including the risk of doing nothing.
• Medicine 3.0 pays far more attention to maintaining healthspan, the quality of life, than lifespan.
• Our longest risk prediction time frame is ten years.
• The future, for most of us, remains a hazy abstraction.
• Aging is not merely the passage of time, but what is happening inside us.
• Someone who drops dead of a heart attack did not just get sick an hour earlier.
• Not everyone who dies in their eighties or nineties passes through the valleys of cognitive, physical, or emotional destruction.
• Our tactics in Medicine 3.0 fall into five broad domains: exercise, nutrition, sleep, emotional health, and exogenous molecules, meaning drugs, hormones, or supplements.
• I now consider exercise to be the most potent longevity “drug” in our arsenal.
• A clinical trial to guide a cardiovascular prevention strategy for a healthy forty-year-old would simply take too long.
• The older you get, the more genes start to matter.
• One in five people in the general population will have received some type of cancer diagnosis by age seventy-two.
• Centenarians have very little in common with one another genetically.
• APOE (apolipoprotein E) is involved in cholesterol transport and processing, and it has three variants: e2, e3, and e4.
• Having one or two copies of the e4 variant seems to multiply one’s risk of developing Alzheimer’s disease by a factor of between two and twelve.
• People who carried at least one copy of APOE e2 (and no e4) were about 30 percent more likely to reach extreme old age than people with the standard e3/ e3 combination.
• Those with two copies of e4, one from each parent, were 81 percent less likely to live that long,
• Variants in a particular gene called FOXO3 (which regulates how other genes are expressed) seem to be directly relevant to human longevity.
• We need to think about very early disease-specific prevention and very early general prevention via common drivers and risk factors.
• Rapamycin had been demonstrated to do something that no other drug had ever done before: extend maximum lifespan in a mammal.
• In 1999 it was approved by the US Food and Drug Administration (FDA) to help transplant patients accept their new organs.
• Rapamycin tends to slow down the process of cellular growth and division.
• mTOR is highly “conserved,” meaning it is found in virtually all forms of life, ranging from yeast to flies to worms and right on up to us humans.
• The job of mTOR is basically to balance an organism’s need to grow and reproduce against the availability of nutrients.
• Resveratrol did not extend lifespan in a diverse population of normal mice when tested by NIA.
• Limiting caloric intake (CR) can lengthen the lifespan of a mouse or a rat by anywhere from 15 to 45 percent,
• Reducing the amount of nutrients available to a cell seems to trigger a group of innate pathways that enhance the cell’s stress resistance and metabolic efficiency.
• Dietary restriction triggers the production of newer, more efficient mitochondria to replace old and damaged ones (via AMPK pathway).
• Autophagy is a form of cellular recycling, cleaning out the accumulated junk in the cell and repurposing it or disposing of it.
• Giving rapamycin daily, as is typically done with transplant patients, appears to inhibit both complexes, while dosing the drug briefly or cyclically inhibits mainly mTORC1.
• what we eat and how we metabolize it appear to play an outsize role in longevity.
• Not everyone who is obese is metabolically unhealthy, and not everyone who is metabolically unhealthy is obese.
• I insist my patients undergo a DEXA scan annually — and I am far more interested in their visceral fat than their total body fat.
• When insulin resistance begins to develop, the train is already well down the track toward type 2 diabetes.
• Today over 11 percent of the US adult population, one in nine, has clinical type 2 diabetes.
• Patients with diabetes have a much greater risk of cardiovascular disease, as well as cancer and Alzheimer’s disease and other dementias.
• Fructose is metabolized in a manner different from other sugars.
• Fructose does not pose a problem when consumed the way that our ancestors did - mostly in the form of actual fruit.
• High uric acid is an early warning sign that we need to address a patient’s metabolic health, their diet, or both.
• But the first thing I look for, the canary in the coal mine of metabolic disorder, is elevated insulin.
• The logical first step in our quest to delay death is to get our metabolic house in order.
• Heart attacks are still fatal roughly one-third of the time.
• American women are up to ten times more likely to die from atherosclerotic disease than from breast cancer.
• If stretched out and laid end to end, our vascular network would wrap around the earth more than twice.
• Cholesterol is required to produce some of the most important structures in the body including cell membranes, hormones and bile acids.
• Each lipoprotein particle is enwrapped by one or more large molecules, called apolipoproteins, that provide structure, stability, and, most importantly solubility to the particle.
• HDL particles are wrapped in a type of molecule called apolipoprotein A (or apoA).
• LDL is encased in apolipoprotein B (or apoB).
• Most of the actual cholesterol that we consume8 in our food ends up being excreted.
• Much of the basic research into cholesterol and atherosclerosis had been conducted in rabbits, which have a unique ability to absorb cholesterol into their blood from their food.
• 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.
• Evidence has piled up pointing to apoB as far more predictive of cardiovascular disease than simply LDL-C.
• Lp(a) may be even more likely than a normal LDL particle to get stuck in the endothelium.
• Lp(a) is the most prevalent hereditary risk factor for heart disease.
• Atherosclerotic disease shouldn’t even be in the top ten causes of death, if we treated it more aggressively.
• Looking at a thirty-year time frame rather than the standard ten years could prevent hundreds of thousands more cardiac events.
• I want to knock someone’s apoB concentration down to 20 or 30 mg/ dL, about where it would be for a child.
• Cancer is the second leading cause of death in the United States.
• Cancer becomes exponentially more prevalent with each decade of life.
• The Cancer Genome Atlas found that each tumor had more than one hundred different mutations, on average, and those mutations almost appeared to be random.
• It is this metastatic cancer that is responsible for most cancer deaths.
• Once cancer has spread, the entire game changes: we need to treat it systemically rather than locally.
• The Warburg effect is how cancer cells fuel their own proliferation.
• Globally, about 12 to 13 percent of all cancer cases are thought to be attributable to obesity.
• 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.
• An immunotherapy is any therapy that tries to boost or harness the patient’s immune system to fight an infection or other condition.
• It needs to be able to distinguish “bad self” (cancer) from “good self” (everything else).
• 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).
• Checkpoint inhibitors help make the cancer visible to the immune system.
• About a third of cancers can be treated with immunotherapy, and of those patients, just one-quarter will actually benefit (i.e., survive).
• Adoptive cell therapy (ACT) effectively means designing a new, customized anticancer drug for each individual patient.
• The ten-year survival rate for patients with metastatic cancer is virtually the same now as it was fifty years ago: zero.
• In my practice we typically encourage average-risk individuals to get a colorectal cancer screening colonoscopy by age forty.
• We can finally see a path to a world where a cancer diagnosis typically means an early detection of a treatable problem rather than a late discovery of a grim one.
• My patients would rather die from cancer or heart disease than lose their minds, their very selves.
• Even when drugs succeed in clearing amyloid or slowing its production, they have yet to show benefit in improving patients’ cognitive function or slowing the progression of Alzheimer’s Disease.
• Close to one in three patients with mild to moderate dementia had no evidence of amyloid in their brains.
• Lewy body dementia and Parkinson’s disease are associated with the accumulation of a neurotoxic protein called alpha-synuclein.
• Multidomain lifestyle-based interventions have improved cognitive performance among at-risk adults.
• Dementia can progress unnoticed for years before any symptoms appear.
• Exercise is the only intervention shown to delay the progression of Parkinson’s.
• People with a history of cardiovascular disease are at a higher risk of developing Alzheimer’s disease.
• Populations with a high prevalence of e4 suggest that it may have been helpful for survival in environments with high levels of infectious disease.
• Hearing loss is clearly associated with Alzheimer’s disease, but it’s not a direct symptom.
• P. gingivalis that commonly causes gum disease, is responsible for large increases in levels of inflammatory markers such as IL-6.
• Four sauna sessions per week seems to be the sweet spot to reduce the risk of Alzheimer’s by about 65 percent.
• I’ve taken care of many thin patients with metabolic problems.
• Study after study has found that regular exercisers live as much as a decade longer than sedentary people.
• An average forty-five-year-old man will have a VO2 max around 40 ml/ kg/ min, while an elite endurance athlete will likely score in the high 60s and above.
• A 2018 study found that higher VO2 max was associated with lower mortality across the board.
• There is no other intervention, drug or otherwise, that can rival this magnitude of benefit from exercise.
• Seniors with the least muscle mass (also known as lean mass) are at the greatest risk of dying from all causes.
• The three dimensions in which we want to optimize our fitness are aerobic endurance and efficiency (aka cardio), strength, and stability.
• I am convinced that it is impossible to be healthy without also having healthy mitochondria.
• Our mitochondria can convert both glucose and fatty acids to energy.
• Fatty acids can be converted to energy only in the mitochondria.
• “Slow-twitch” muscle fibers are extremely dense with mitochondria.
• Zone 2 is the maximum level of effort that we can maintain without accumulating lactate.
• One of the most significant hallmarks of aging is a decline in the number and quality of our mitochondria.
• Exercise enables the body to essentially bypass insulin resistance in the muscles to draw down blood glucose levels via NIMGU.
• 2 watts/ kg is about the zone 2 output that one would expect from a reasonably fit person.
• VO2 max is a pretty good proxy measure of our physical capability.
• Boosting elderly subjects’ VO2 max by 6 ml/ kg/ min, or about 25 percent, was equivalent to subtracting twelve years from their age.
• It’s never too late to improve your VO2 max.
• It is very difficult to put on muscle mass later in life.
• We measure bone mineral density (BMD) in every patient, every year, looking at both of their hips and their lumbar spine using DEXA.
• Bone density peaks as early as our late twenties before beginning a slow, steady decline.
• I still incorporate some kind of carrying, typically with dumbbells, kettlebells, or sandbags, into most of my workouts.
• There is an enormous body of literature linking better grip strength in midlife and beyond to decreased risk of overall mortality.
• American adults actually seem to have far weaker grip strength - and thus less muscle mass - than they did even a generation ago.
• Most adults can’t squat correctly, even without any added weight.
• Deep, steady breathing activates the calming parasympathetic nervous system,
• Someone’s breathing style gives us insight into their broader stability strategy.
• The ability to balance on one leg at ages fifty and older has been correlated with future longevity.
• Stability is about safe and powerful transmission of force through muscles and bones, and not joints or spinal hinge points.
• We discourage patients from becoming overly reliant on [personal] trainers.
• We actually don’t know that much about how what we eat affects our health.
• Instead of diet, we should be talking about nutritional biochemistry.
• Wearing a cast on a broken bone will allow it to heal. Wearing a cast on a perfectly normal arm will cause it to atrophy.
• Epidemiology is incapable of distinguishing between correlation and causation.
• Humans are terrible study subjects for nutrition.
• Very few published epidemiological studies show a risk increase of even 50 percent (HR = 1.50) for any given type of food.
• Study results sometimes reflect the baseline health of the subjects more than the influence of whatever input is being studied.
• Once you remove the effects of other factors that may accompany moderate drinking— such as lower BMI, affluence, and not smoking— any observed benefit of alcohol consumption completely disappears.
• In the PREDIMED study, the group receiving olive oil had about a one-third lower incidence (31 percent) of stroke, heart attack, and death than the low-fat group.
• Perhaps the most vexing issue with diet and nutrition studies is the degree of variation between individuals.
• The leading source of calories that Americans consume is a category called “grain-based desserts,” like pies, cakes, and cookies.
• People who count their calories and limit them can and do lose weight.
• The quality of your diet may matter as much as the quantity.
• Any form of dietary restriction (DR) that restricts protein, for example, is probably a bad idea for most people, because it likely also impairs the maintenance or growth of muscle.
• Alcohol serves no nutritional or health purpose.
• In digestion, most carbohydrates are broken down to glucose, which is consumed by all cells to create energy in the form of ATP.
• CGM gives continuous, real-time information on blood glucose levels.
• Real-time blood glucose serves as a decent proxy for the insulin response.
• We want to lower average blood glucose and reduce the amount of variability from day to day and hour to hour.
• I like to keep average glucose at or below 100 mg/ dL, with a standard deviation of less than 15 mg/ dL.
• 100 mg/dL corresponds to an HbA1c of 5.1 percent.
• 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.
• Carbohydrate tolerance is heavily influenced by other factors, especially your activity level and sleep.
• Don’t be alarmed by glucose spikes when you are exercising.
• Protein and amino acids are the essential building blocks of life.
• Elderly people consuming the RDA of protein (0.8 g/ kg/ day) end up losing muscle mass,
• For active people with normal kidney function, one gram per pound of body weight per day19 (or 2.2 g/ kg/ day) is a good place to start.
• The overall quality of protein derived from plants is significantly lower than that from animal products.
• Be sure to get about three to four grams per day of leucine and lycine and at least one gram per day of methionine.
• Eating protein also helps us feel satiated, inhibiting the release of the hunger-inducing hormone ghrelin.
• Virtually no food belongs to just one group of fats (i.e. PUFA, MUFA, or SFA).
• We look for between 8 and 12 percent of RBC membrane composed of EPA and DHA.
• Recent metastudies have found that increasing PUFA probably makes little or no difference (neither benefit nor harm) to our risk of death and reducing saturated fat has little or no effect on all-cause mortality or cardiovascular mortality.
• Subtle changes in fat intake, particularly of saturated fats, can make a significant difference in lipid levels in some people.
• The scientific literature on fasting is still relatively weak.
• A sixteen-hour fast for a mouse is akin to a multiday fast for a human.
• A 2020 clinical trial found no weight loss or cardiometabolic benefits in a group of 116 volunteers on a 16/ 8 eating pattern.
• Fasting might cause some people, especially lean people, to lose too much muscle.
• Bad nutrition can hurt us more than good nutrition can help us.
• One sleepless night can create a state that is the functional equivalent of being legally drunk.
• Every animal engages in some fom of sleep.
• We need to sleep about seven and a half to eight and a half hours a night.
• Sleep deprivation can cause profound insulin resistance.
• People who sleep eleven hours or more nightly have a nearly 50 percent higher risk of all-cause mortality.
• When we sleep poorly, we can be desperately, irrationally hungry the next day.
• Less than six hours a night) is associated with about a 6 to 26 percent increase in cardiovascular disease.
• People who have generally slept less than seven hours per night, over decades, tend to have much more amyloid-beta and tau built up in their brains.
• Successfully treating sleep disturbance may delay the age of onset into mild cognitive impairment (MCI) by about eleven years.
• Sleep medications such as Ambien and Lunesta do not promote healthy, long-lasting sleep so much as they tend to promote a sleep-like state of unconsciousness.
• One drug that we do find helpful for assisting with sleep is trazodone.
• The first requirement for good sleep is darkness.
• Over the course of the day, adenosine builds up in our brain, creating what scientists call “sleep pressure,” or the drive to sleep.
• Emotional health and physical health are closely intertwined.
• About as many Americans died from drug overdoses as died from diabetes in 2021/2.
• Emotional health, which incorporates mental health but is also much broader—and less easy to codify and categorize.
• Clinical trials have found dialectical behavior therapy, or DBT, to be effective in helping suicidal and self-harming patients.
• You do not need to wait for your mood to improve to make a behavior change.
• Exposing oneself to the fractal geometric patterns in nature can reduce physiological stress.
• 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.