Outlive

Outlive: The science and art of longevity (Peter Attia)

  • Fantastic! One of the best books Ive read in years. Changed my life.
  • Longevity does not mean living forever. Or even to 120 or 150.
  • Four Horseman: heart disease, cancer, neurodegenerative disease, and type-2 diabetes and related metabolic dysfunction.
  • Healthspan is defined as the period of life when we are free from disability or disease.
  • The only way to create a better future for yourself is to start thinking about it and taking action NOW
  • Medical training is much more effective against fast death than slow death
  • Death rates from cancer have hardly budged in the more than 50 years since the war on cancer was declared. While the prevalence of each of the Horseman increases sharply with age, they typically begin much earlier than we recognize, and they usually take a very long time to kill you.
  • None of our treatments for late-stage lung cancer has reduced mortality by nearly as much as the worldwide reductin in smoking. This simple preventive measure has save more lives than any late-stage intervention. Yet mainstream medicine still insists on waiting until the point of diagnosis before we intervene.
  • The time to intervene is well before the patient gets anywhere near having type-2 diabetes; even prediabetes is very late in the game. It is absurd and harmful to treat this disease like a cold or a broken bone.

  • Modern medicine does not really have a handle on when and how to treat the chronic diseases of aging that will likely kill most of us.

    This big suprise is that this is actually good news for us, in a way. Each one of the horseman is cumulative, the product of multiple risk factors adding up and componding over time. Many of the individual risk factors are relatively easy to reduce or even eliminate. Even better, the four horseman share certain features in common that make them volnerable to some of the same tactics.

  • Medicines biggest failing is in attempting to treat all these conditions at the wrong end of the timescale – after they are entrenched – rather than before they take root. As a result, we ignore imprtant warning signs and miss opportunities to intervene at a point where we still have a chance to beat back these diseases, improve health, and potentially extend lifespan.
  • The typical panel that you receive is misleading and oversimplified to the point of uselessness.
  • 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. Most people dont do nearly enough and exercising the wrong way can do as much harm as good.

  • Why doesn the world need another book about longevity? Most writers in this space fall into certain categories:

    True believers: Following a specific diet is all you need. They lack is scientific rigor which they make up for with passion. Reprogramers: those that are convinced that science will soon figure out how to unplug from the aging process. This seems highly unlikely in our lifetimes. We need to hedge our bets in case this highfalutin science somehow fails to put longevity into a pill. Peters role: not a lab scientist or clinical researcher, but more of a translator. We already know more than enough to bend the curve.

  • Outlive means living longer and living better.
  • Goal: to create an actionable operating manual for the practice of logevity. With time and effort you can extend your lifespan by a decade and your healthspan possibly by two, meaning you might hope to function like someone 20 years younger.
  • The intent is not to tell you exactly what to do; its to help you learn how to think about doing these things.

  • Longevity demands a paradigm-shifting approach to medicine. Not "preventive" medicine; its "proactive" medicine This has the potential to change the live of individuals and relieve vast amounts of suffering in our society This change is not coming from the medical establishment; it will happen only if and when patients and physicians demand it.

    Nearly all the money flows to treatment rather than prevention

  • Medicine 1.0: direct observation abetted more or less by guess work Medicine 2.0: mid 19-C with the advent of the germ theory of disease Medicine 3.0: goal not to patch people up and get the out the door, but to prevent the tumors from appearing in the first place.

  • Understanding risk is a huge blind spot in medicine. In Medicine 3.0 our starting point is the honest assessment and acceptance of risk – including the risk of doing nothing.

    A 40 year old should be concertned with her 30 or 40-year cardiovascular risk profile.

  • Medicine 3.0 demands much more from you, the patient: You must be well-informed, medically literate, clear-eyed about your goals, and cognizant of the true nature of risk.
  • Drs have relied on two tests to gauge patients metabolic health: a fasting glucose test, or the HbA1c test
  • a fundamental concept in this approach to longevity is the need to thin about and plan for the later decades of our life.
  • Squaring the longevity curve: live longer and live better for longer
  • While death is inevitable, deterioration is less so. No everyone who dies in their 80s or 90s passes throught the valleys of cognitive, physical, or emotional destruction.
  • Actions we take to improve our healthspan will almost always result in a longer lifespan. our tactics are largely aimed at improving healthspan first; the lifespan benifits will follow.
  • Tactics for Medicine 3.0 fall in five broad domains: -) exercise -) nutrition -) sleep -) emotional health -) exogenous molecules
  • What you eat matters, but the first-order term is how much you eat: how many calories you put in your body
  • It is important that our strategy be based on evidence. Unfortunately the pursuit of longevity is where the most powerful tool of Medicine 2.0, the randomized control trail, runs into a brick wall. The purists of evidence-based medicine demand data from RCTs before doing anything, but the time horizon of a RCT is a major limitation.
  • Option B: look at the different types of data that we do have and develop a strategy to triangulate between them. combine insights from five different sources of data, that, viewed separately, probably arent strong enought to act on. When taken together, however, they can provide a solid foundation for our tactics. Our framework must shift from exclusively evidence-based to evidence-informed, risk-adjusted precision medicine.
  • Rule of thumb: if a given intervention can be shown to extend lifespan and healthspan in multiple species spanning a billion years of evolution, eg: worms to monkeys, then I am inclidec to take it seriously.
  • for every supercentenarian (>110) in the world thare are about nine billionaires
  • It appears that no two centenarians follow the same genetic path to reaching extreme old age. There are many ways to achieve longevity.
  • Medicine 3.0:
    • I test all my patients for their APOE genotype
    • I insist my patients undergo a DEXA scan annually - I am far more insterested in their visceral fat than their total body fat.
    • I test my patients levels of uric acid, not only b/c high level may promote fat storage, but also becuase it is linked to high blood pressure. High uric acid is an early warning sign that we need to address a patients metabolic health
    • I watch the ratio of triglycerides to HDL cholesterol (should be less than 2:1 or better 1:1) as well as VLDL
    • One test I like to give patients is the oral glucose tolerance test, a patient swallows a sweet beverage and we measure the patients glucose and their insulin every 30min for 2 hours
    • I have all my patients tested for apoB regularly, and you should ask for the same test the next time you see your doctor. I take a very hard line on lowering apoB, the particle that causes all the trouble (get it as low as possible, as early as possible)
    • Lp(a) is the first thing I look for. It is the most prevalent hereditary risk factor for heart disease. You should definitely ask for a Lp(a) test.
    • We measure BMD in every patient, every year, looking at both of their hips and their lumbar spine using DEXA
  • When food is plentiful mTOR is activated and the cell goes into growth mode, producing new proteins and undergoing cell division. When nutrients are scarce, mTOR is suppressed and cells go into a kind of "recycling" mode, breaking down cellular components and generally cleaning house.
  • Rapamycin: no other molecule has been shown to extend lifespan in a mammal. Ever.
  • Restricting the amount of nutrients tat are available, via dietary restriction or exercise, triggers the production of newer, more efficient mitochondria to replace old and damaged ones.
  • 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.
  • Medicine 2.0 does not recognize "slowing aging" and "delaying disease" as fully legitimate end points. If were talking about preventing the diseases of aging, which kill 80% of us, then its worth having a serious conversation about what level of risk is acceptable in order to use rapamycin to stay healthy.
  • In terms of reccomended ranges, "Normal" is not the same as "healty". The refernce ranges for these tests are based on current percentiles, but as the population in general becomes less healthy, the average may diverge from the optimal levels.
  • Metabolic Syndrom:
    • high blood pressure (>130/80)
    • high triglycerides (>150 mg/dL)
    • low HDL cholesterol (<40 mg/dL)
    • central adiposity (belly fat)
    • elevated fasting glucose (>110 mg/dL)
  • Why wait until someone has three of the five markers? Any one of them is generally a bad sign.
  • Fructose is rich in energy, but it tricks our metabolism into thinking that we are depleting energy – and need to take in still more food and store more energy as fat.
  • Consuming large quantities of liquid fructose simply overwhelms the ablility 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.
  • The first think I look for, the canary in the coal mine of metabolic disorder is insulin.
  • It is beyond backwards that we dont treat hyperinsulinemis like a bona fide endocrine disorder of its own. Doing so might have a greater impact on health and longevity than any other target of therapy
  • The logical first step in our quest to delay death is to get our metabolc house in order.
  • CT scans can be calibrate to detect calcification in coronary arteries, a sign of advanced atherosclerosis. A more advanced type of CT scan, called a CT aniogram, which I much prefer to a garden-variety calcium scan because it can also identify "soft" plaque.
  • Heart diseases remains our deadliest killer, the worst of the Horseman. With the right strategy and attention to the correct risk factors (at the correct time) it should be possible to eliminate much of the associated morbidity and mortality. This should be the 10th leading cause of death not the first.
  • Our blood transports oxygen and nutrients to our tissues and carries away waste. It also traffics cholesterol molecules between cells.
  • Cholesterol is essential to life. It is required to produce some of the most important structures in the body: cell membranes and hormones. All cells can make thier own cholesterol, but 20% of the bodies supply is found in the liver.

  • Another major misconception about heart disease is that it is somehow caused by the cholesterol that we eat in our diet. Most of the cholesterol we consume in our foods is excreted. The vast majority of the cholesterol in our circulation is actually poduced by our own cells.

    "There is no connection whatsoever between cholesterol in our food and in our blood" "None. And we've known that all along. Cholesterol is the diet doesnt matter unless you happen to be a chicken or a rabbit"

  • We have to know how many of these apoB particles are circulating in your bloodstream. That number is much more relevant that the total quantity of cholesterol that these particles are carrying.
  • The all important "good cholesterol" HDL-C doesnt actually tell me very much if anything about your overall risk profile.
  • Simply put, I think you cant lower apoB and LDL-C too much, provided there are no side effects from treatment. You want it as low as possible.

  • Atherosclerosis is with us, in some form, throughout our life course. Yet most doctors consider it "overtreatment" to intervene if a patients computed ten year rist of a major adverse cadiac event is below 5%. This betrays a broader ignorance about theinexorable, long-term unfolding of heart disease. Ten years is far too short a time horizon. If we want to reduce deaths from cardiovascular disease, we need to begin thinking about prevention in people in thier 40s and even 30s. If our time horizon is "the rest of your life", then nobody is at low risk.

    We know that smoking causes lung cancer. Should we tell someone to stop smoking only after thier 10 year risk of lung cancer reaches a certian threshold? Do we think its OK for people to keep smoking until they are 65 and then quit?

  • Cancer is the 2nd leading cause of death in the US right behind heart disease. Cancer still kills Americans at almost exactly the same rate as it did 50 years ago.
  • We still know relatively little about how cancer begins and why it spreads. Caner cells dont grow faster than their noncancerious counterparts; they just dont stop growing when they are supposed to.
  • Solid organ tumors typically kill you only when they speard to other organs. We dont know what causes cancer to spread; only about 5% of the US cancer research funding goes to the study of spreading cancer.
  • Contrary to popular belief, killing cancer cells is actually pretty easy, selective killing is what is hard.
  • Excess weight is a leading risk factor for cancer, second only to smoking.
  • First rule of cancer: "Dont get cancer" Second rule of cancer" "Catch it as soon as possible"
  • This is why I advocate for early screening. Its a simple truth that treating smaller tumors with fewer mutations is far easier than if we wait for the cancer to advance and potentially acquire murations that help it evade our treatments.
  • Many Drs shy away from APOE gene testing. The conventional wisdom hold that someone with high-risk e4 allele is all but gauranteed to develop Alzheimers disease, and there is nothing we can do for them. So why burden the patient with this terrible knowledge?
  • Exercise is the only intervention shown to delay the progression of Parkinsons.
  • In medicine 3.0 we have five tactical domains that we can address in order to alter someone health. The first is exercise, which I consider to be by far the most potent domain in terms of its impact on both lifespan and healthspan.
  • Study after study has found that regular exercisers live as much as a decade longer than sedentary people.
  • The data demonstrating the effectiveness of exercise on lifespan are as close to irrefutable as one can find in all of human biology
  • Just as with V02-max it is important to maintain muscle mass at all costs.
  • Exercise gets little more than lip service from Medicine 2.0: When was the last time your doctor tested your grip strength or aked you a detailed question about your strength training? Does you doctor know your VO2max ? or have they offered training suggestions for how to improve it ?
  • Three domensions in which we want to optimize our fitness are aerobin endurance and efficiency (aka cardio), strength training, and stability.
  • Aerobic exercise, done in a very specific way, improves our ability to utilize glucose and especially fat as fuel. The healthier and more efficientyour mitochondria, the greater your ability to utilize fat, which is by far the bodies most efficient and abundant fuel source.
  • Training aerobic endurance and efficient (Zone 2: a pace somewhere between easy and moderate.) is the first elemet of my training program.
  • VO2 max intervals are 3 - 8 minutes and a notch less intense than an high-intensity interval. A single VO2 max workout per week will probably suffice
  • If you really stop to consider the kinf of aerobic fitness that most people actually need in the course of their lives, it basically boils down to being really good at going slow for a long time, but also able to go hard and fast when needed.
  • Strength training, especially with heavy weights, stimulates the growth of bone.
  • The most important measure of strength is how much heavy stuff you can carry, not how muscular you are. No other animal is capable of carrying large objects from one place to another with any efficiency
  • I structure my training around exercises that improve the following:
    • Grip strength: classic farmers carry. can you carry have their body weight in each hand (so full body weights in tota) for at least on minute? dead hang for two minutes (this is onle a once in a while test.)
    • attention to both concentric and eccentric loading for all movements: means focusing on the "down" phase of lifts
    • Pulling motions
    • high-hinging movements
  • Pushing onceself hard with out adequate stability, almost inevitable leads to injury. If you are struggling to get thorugh your workout, then you are likely resorting to you body's own "cheats", your ingrained dangerous movement patterns.
  • "How we breath is who we are"

  • An ideal inhalation expands this entire rib cage – front, sides and back – while the belly expands at the same time, allowing the respiratory and pelvic diaphragm to descend. The telltale is that it is quiet. Now, exhale fully though pursed lips for maximum compression and air resistance, to strengthen the diaphragm.

    Repeat the process for five breaths and do two to three sets.

    I practice this "360 degree" breathing everyday, not only in the gym, but also while I am at my desk.

  • www.peterattiamd.com/outlive/videos
  • Balance is the real challenge with swimming, because our center of mass is way off from our center of volume, cause our hips to sink.

  • 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 on social media.

    We have made-for-clickbait epidemiological "studies" that make absurd claims.

    On the other hand, we have clinical trials that tend almost without exception to be flawed. Thnaks to the poor quality of the science, we actually dont know that much about how what we eat affects our health.

    Most people spend either too little or too much time thinking about this topic.

    I am not a dogmoatic advocate of any particular way of eating or form of fasting.

    Food molecules: nothing more than different arrangements of carbon, nitrogen oxygen, phosphorus and hydrogen atoms.

    Instead of diet we should be talking about nutritional biochemistry.

  • The correlation between poor metablic health and being overnourished and undermuscled is very high. Hense, 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 colories while also increasing their protien intake, and to pair this with proper exercise. This is the most common problem we are trying to solve around nutrition.

  • Nutrition is relatively simple, actually. It boils down to a ew basic rules: -) Dont eat too many calories, or too few; -) consume sufficient protien and essential fats; -) obtain the vitamins and minerals you need -) avoid pathogens

    Beyond that we know relatively little with complete certainty. Read that sentence again, please.

  • In nutrition: too many people are majoring in the minor and minoring in the major, focusing too much attentino on small questions while all but ignoring the bigger issues. Small variations in what we eat probably matter a lot less than most people assume.

  • Food is so complexx that epidemiology is simply not up to the task of disentangling the effect of any individual nutrient or food.

    "Nutritional epidemiology is a scandal, It should just go into the waste bin"

    It is extremely easy to be misled by epidemiology: General health is a massive confounder in these studies

  • Compliance is the key issue in nutrition reseach, and with diets in general.
  • The Standard American Diet (SAD) is on one level brilliant. It is a solution to four problems that have plagued humanity since the beginning:
    1. how to produce enough food to feed almost everyone
    2. how to do so inexpensively
    3. how to preserve that food so it can be stored and transported
    4. how to make it highly palatable.
  • Most people on TR diets end up very protein deficient.
  • The balance of our nonalcohol diet consists of carbohydrates, protien, and fat, and its largely a job of finding the right mix for you as an individual.

  • CGM is a gool to help us understand our own individual carb tolerance. It is a huge improvement over the Medicine 2.0 standard of one fasting glucose test per year (which tells you almost nothing of value)

    CGM allows you to view your response to carbs in ral time and make changes rapidly to flatten the curve and lower the average.

    We want to lower average blood glucose and reduce the amount of variability from day to day and hour to hour.

    Overall try to keep the average glucose at or below 100 mg/dL with a standard deviation of less than 15 mg/dL

    If your glucose ramps up from eg: 80 to 110 at night, you are most likely dealing with psychological stress.

  • Everyone tends to be more insulin sensitive in the morning, so it makes sense to frout load our cabs.
  • Nonstarchy veggies such as spinach or broccoli have virtually no impact on blood sugar. Have at them.
  • 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.
  • Unlike carbs and fat, protein is not a primary source of energy. If you consume more protein than you can synthesize into lean mass, you will simply excrete the excess in you urine as urea.

  • The first think you need to know about protien is that the standard recommendation for daily consumption are a joke. IF someone weighs 180 pounds, they really need to consume 130g grams of protein/day ideally closer to 180g.

    THis is a lot of protein to eat, and the added challenge is that it should not be taken in one sitting but rather spread out over the day to avoid losing amino acids to oxidation

  • Multilple studies suggest that the more protein we consume the better.
  • Fasting triggers many of the physiolocgicaland cellular mechanisms that we want to see.
  • Most people cant safely lose muscle mass, so fasting is a tool that we can only really use in extremis, when there are no other viable options.
  • Bad nutrition can hurt us more than good nutrition can help.Protein is the most important macronutrient, the one that should not be compromised Most people will be overnourished – but also under muscled. It is counterproductive for them to limit calories a tthe expense of protein and hence muscle.
  • Poor sleep dramatically increases ones propensity for metabolic dysfunction.
  • Good sleep is like a performance enhancing drug.
  • Do NOT bring your laptop or phone into bed with you.
  • Most of male rage is helplessness masquerading as frustration.
  • "Resume virtues vs eulogy virtues"
  • Try to find joy in being rather than doing.
  • Longevity is meaningless if your life sucks

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