## Metadata - Author: [[Peter Attia MD]] - Full Title: Outlive - Category: #books - Document Tags: [[health]] ## Highlights - There comes a point where we need to stop just pulling people out of the river. We need to go upstream and find out why they’re falling in. —Bishop Desmond Tutu ([Location 109](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=109)) - that death comes at two speeds: fast and slow. ([Location 131](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=131)) - Nor does longevity mean merely notching more and more birthdays as we slowly wither away. This is what happened to a hapless mythical Greek named Tithonus, who asked the gods for eternal life. To his joy, the gods granted his wish. But because he forgot to ask for eternal youth as well, his body continued to decay. Oops. Most of my ([Location 153](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=153)) - The first is how long you live, your chronological lifespan, but the second and equally important part is how well you live—the quality of your years. This is called healthspan, and it is what Tithonus forgot to ask for. ([Location 166](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=166)) - Healthspan is typically defined as the period of life when we are free from disability or disease, but I find this too simplistic. I’m as free from “disability and disease” as when I was a twenty-five-year-old medical student, but my twenty-something self could run circles around fifty-year-old me, both physically and mentally. That’s just a fact. Thus the second part of our plan for longevity is to maintain and improve our physical and mental function. ([Location 168](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=168)) - The key question is, Where am I headed from here? What’s my future ([Location 171](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=171)) - Tags: [[orange]] - This ethos is ingrained in anyone who goes into medicine: nobody dies on my watch. We approached our cancer patients in the same way. ([Location 191](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=191)) - 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 ([Location 201](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=201)) - Medicine’s 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. ([Location 264](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=264)) - Unfortunately, in today’s unhealthy society, “normal” or “average” is not the same as “optimal.” ([Location 274](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=274)) - One macronutrient, in particular, demands more of our attention than most people realize: not carbs, not fat, but protein becomes critically important as we age. ([Location 279](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=279)) - 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. But most people don’t do nearly enough—and exercising the wrong way can do as much harm as good. ([Location 280](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=280)) - Tags: [[pink]] - Finally, as I learned the hard way, striving for physical health and longevity is meaningless if we ignore our emotional health. Emotional suffering can decimate our health on all fronts, and it must be addressed. ([Location 282](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=282)) - Tags: [[orange]] - The time to repair the roof is when the sun is shining. —John F. Kennedy ([Location 322](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=322)) - I watched the five stages of grief described by Elisabeth Kübler-Ross in her classic book On Death and Dying—denial, anger, bargaining, sadness, and acceptance—flash ([Location 368](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=368)) - Tags: [[blue]] - This technology, known as continuous glucose monitoring (CGM), lets me observe how their individual metabolism responds to a certain eating pattern and make changes to their diet quickly. ([Location 501](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=501)) - First, Medicine 3.0 places a far greater emphasis on prevention than treatment. ([Location 505](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=505)) - This is where most people make a wrong turn. They want to take a shortcut, right to the tactics: this is what to eat (and not eat), that is how you should exercise, these are the supplements or medications you need, and so on. ([Location 667](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=667)) - the Sun Tzu quote that opens this chapter: “Tactics without strategy is the noise before defeat.” ([Location 670](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=670)) - 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. Our specific tactics flow from our strategy, and the strategy derives from our objective. We know what the objective is by now, but the strategy is the key to victory. ([Location 672](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=672)) - Tags: [[blue]] - ring. In this book, we will apply this three-part approach to longevity: objective → strategy → tactics. ([Location 694](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=694)) - Tags: [[pink]] - passes. Entropy is working on us every single day. ([Location 707](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=707)) - “Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death,” wrote the authors of an influential 2013 paper describing what they termed the “hallmarks of aging.” ([Location 707](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=707)) - it. Lifespan deals with death, which is binary: you’re alive, and then you’re dead. It’s final. ([Location 729](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=729)) - Typically, Medicine 2.0 steps in only when something is acutely wrong, like an infection or a broken bone, with short-term fixes for the immediate problem. In Medicine 3.0, our tactics must become interwoven into our daily lives. We eat, breathe, and sleep them—literally. ([Location 775](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=775)) - Our tactics in Medicine 3.0 fall into five broad domains: exercise, nutrition, sleep, emotional health, and exogenous molecules, meaning drugs, hormones, or supplements. ([Location 778](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=778)) - “Isn’t it ironic that your entire professional life is predicated around trying to make people live longer,” she mused, “yet you’re putting no energy into being less miserable, into suffering less emotionally?” ([Location 816](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=816)) - Whiskey’s a good medicine. It keeps your muscles tender. —Richard Overton, 1906–2018 ([Location 914](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=914)) - Not to be outdone, British World War I veteran Henry Allingham attributed his own 113-year lifespan to “cigarettes, whiskey, and wild, wild women.” ([Location 918](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=918)) - title, “The Older You Get, the Healthier You Have Been.” ([Location 1009](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1009)) - In mathematical terms, the centenarians’ genes have bought them a phase shift in time—that is, their entire lifespan and healthspan curve has been shifted a decade or two (or three!) to the right. Not only do they live longer, but these are people who have been healthier than their peers, and biologically younger than them, for virtually their entire lives. ([Location 1009](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1009)) - Tags: [[blue]] - pool. In short, natural selection doesn’t care if we develop Alzheimer’s disease (or baldness) in old age. It doesn’t affect our reproductive fitness. By the time dementia would appear, we have likely already handed down our genes. ([Location 1046](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1046)) - way. Indeed, there is a chance that those same genes may have conferred some sort of advantage earlier in life, a phenomenon known as “antagonistic pleiotropy.” ([Location 1049](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1049)) - Tags: [[pink]] - You may have heard of this gene, which is called APOE, because of its known effect on Alzheimer’s disease risk. It codes for a protein called APOE (apolipoprotein E) that is involved in cholesterol transport and processing, and it has three variants: ([Location 1058](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1058)) - e2, e3, and e4. Of these, e3 is the most common by far, but 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. ([Location 1060](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1060)) - Scientists who play by someone else’s rules don’t have much chance of making discoveries. —Jack Horner ([Location 1145](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1145)) - rapamycin, ([Location 1158](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1158)) - Tags: [[orange]] - Note: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/ - David Sabatini, ([Location 1161](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1161)) - Tags: [[blue]] - Note: https://en.wikipedia.org/wiki/David_M._Sabatini - (mycin is the suffix typically applied to antimicrobial agents). ([Location 1182](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1182)) - mTOR (pronounced “em-tor”), for “mechanistic target of rapamycin.”[*2] ([Location 1204](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1204)) - Case in point: the well-publicized finding from 2006 that a substance found in the skins of grapes (and in red wine), resveratrol, extended lifespan in overweight mice. ([Location 1233](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1233)) - other well-hyped supplements such as nicotinamide riboside, or NR: it, too, failed to extend lifespan consistently in mice. ([Location 1238](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1238)) - Consider that five grams of glucose, spread out across one’s entire circulatory system, is normal, while seven grams—a teaspoon and a half—means you have diabetes. As I said, the liver is an amazing organ. ([Location 1540](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1540)) - Where subcutaneous fat is thought to be relatively harmless, this “visceral fat” is anything but. These fat cells secrete inflammatory cytokines such as TNF-alpha and IL-6, key markers and drivers of inflammation, in close proximity to your most important bodily organs. This may be why visceral fat is linked to increased risk of both cancer and cardiovascular disease. ([Location 1572](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1572)) - Evolution is no longer our friend, because our environment has changed much faster than our genome ever could. Evolution wants us to get fat when nutrients are abundant: the more energy we could store, in our ancestral past, the greater our chances of survival and successful reproduction. We needed to be able to endure periods of time without much food, and natural selection obliged, endowing us with genes that helped us conserve and store energy in the form of fat. That enabled our distant ancestors to survive periods of famine, cold climates, ([Location 1647](https://readwise.io/to_kindle?action=open&asin=B0B1BTJLJN&location=1647))