Outlive by Peter Attia

Outlive was one of the books we gave to our investors for 2023, part of a collection coupled to our investment theses. After reading a book, I transcribe the most interesting passages so that I can remember them… enjoy!

TLDR; “The data are unambiguous: exercise not only delays actual death but also prevents both cognitive and physical decline, better than any other intervention.” (p.48)

“More than any tactical domain we will discuss in this book, exercise has the greatest power to determine how you will live out the rest of your life. Study after study has found that regular exercisers live as much as a decade longer than sedentary people. And if exercise is not part of your life at the moment, you are not alone — 77% of the U.S. population is like you. Now is the time to change that. Right now. Going from zero weekly exercise to just 90 minutes per week can reduce your risk from dying from all causes by 14%. It’s very hard to find a drug that can do that.” (218).

“Cardiorespiratory fitness is inversely associated to long-term mortality, with no observed upper limit of benefit. Extremely high aerobic fitness was associated with the greatest survival.” (223)

We recently invested in an oral APMK-activator: “AMPK is activated when we exercise, responding to the transient drop in nutrient levels. AMPK prompts the cell to conserve and seek alternative sources of energy. It does this first by stimulating the production of new mitochondria, the tiny organelles that produce energy in the cell, via a process called mitochondrial biogenesis. These fresh mitochondria help the cell produce more ATP, the cellular energy currency, with the fuel it does have. More importantly, AMPK works to inhibit the activity of mTOR, the cellular growth regulator” (82). So, the hope is that it might have similar weight loss effects as Wegovy while also extending lifespan like Rapamycin.

“Mitochondrial health becomes especially important as we grow older, because one of the most significant hallmarks of aging is a decline in the number and quality of our mitochondria. But the decline is not necessarily a one-way street. Mitochondria are incredibly plastic, and when we do aerobic exercise, it simulates the production of many new and more efficient mitochondria. [see AMPK above] As we create more mitochondria, we greatly increase out capacity to dispose of glycogen, rather than having it end up as fat or remaining in our plasma.” (242)

“Bone density diminishes on a parallel trajectory to muscle mass. Why do we care so much? Just as with muscle, it comes down to protection. One third of people over 65 who fracture their hip are dead within a year.” (254)

“Many studies suggest that grip strength—literally how hard you can squeeze something with one hand—predicts how long you are likely to live” (258)

Fat storage capacity: “Even a relatively lean adult may carry 10kg of fat in their body, representing a whopping 90,000 calories of stored energy.” (96)

“Nearly half of the U.S. population is either on the road to type 2 diabetes or already there.” (103)

Beware liquid sugars, especially soft drinks and fruit juice: “One abundant source of calories in our present diet, fructose, also turns out to be a very powerful driver of metabolic dysfunction if consumed to excess. It’s the form of sugar found in nearly all fruits, and as such, it is essential to the diets of many species. But as it turns out, we humans have a unique capacity for turning calories from fructose into fat. The story is complicated but fascinating. The key factor here is that fructose is metabolized in a manner different from other sugars.” (104)

“If there was one type of food I would eliminate from everyone’s diet, if I could, it would be sodas and fruit juices” (347)

“Globally, cerebrovascular disease (heart disease and stroke) represents the leading cause of death. It’s not just men that are at risk: American women are 10x more likely to die from atherosclerotic disease than from breast cancer (not a typo, one in three versus one in thirty). It is also more easily prevented than either cancer or Alzheimer’s disease. Bluntly put: this should be the tenth leading cause of death, not the first.” (115)

“There is no connection whatsoever between cholesterol in food and cholesterol in blood. None. And we’ve known that all along. Cholesterol in the diet doesn’t matter at all unless you happen to be a chicken or a rabbit.” (118)

Good fats: “Monounsaturated fats, found in high quantities in extra virgin olive oil, nuts and avocados… I push my patients to consume more of these, up to 60% of total fat intake.” (133)

Cancer: “With a few exceptions, solid organ tumors typically kill you only when they spread to other organs. Breast cancer and prostate cancer kills only when it becomes metastatic. But what causes cancer to spread? Only 5 to 8% of U.S. cancer research funding goes to the study of metastasis.” (147) We have a recent investment focused on this.

Colonoscopy — early and often: “Of all the major cancers, colorectal cancer is one of the easiest to detect, with the greatest payoff in terms of risk reduction.” (170)

Avoiding Alzheimer’s: DHA from fish oil, flossing (yes, flossing), dry sauna and deep sleep are protective. But “type 2 diabetes doubles or triples your risk of developing Alzheimer’s disease.” (196)

Cherish your sleep: “Even in the short term, sleep deprivation can cause profound insulin resistance. This turns out to be the one of the most consistent findings in all of sleep research.” (357)

“REM sleep seems to protect our emotional equilibrium, while helping us process memories. Deep sleep, on the other hand, seems to be essential to the very health of our brain as an organ. While we are in deep sleep, our brain activates a kind of internal waste disposal system that allows cerebrospinal fluid to flood in between the neurons and sweep away the intercellular junk; while this happens, the neurons themselves pull back to allow this happen. This cleansing process flushes out detritus, including both amyloid-beta and tau, the two proteins linked to neurodegeneration.” (362)

“One study linked poor sleep quality in cognitively normal people with the onset of cognitive impairment—just one year later.” (363)

Attia’s advice: avoid screens at night, LED clocks, any light in room, alcohol or caffeine in the afternoon, keep it cold (65°F) at bedtime, avoid Ambien.

He closes with a personal journey and plea for emotional health: “Emotional health may represent the most important component of healthspan. Deaths of despair have actually diminished life expectancy for some segments of the American population—the first time this has happened in more than a century. The substance abuse crisis has created a longevity crisis, because it is really a mental health crisis in disguise.” (382)

“Yes, a mindfulness meditation practice can make this all easier. Yes, MDMA and psilocybin, when used with skilled guidance and in the correct setting, can be powerful; I have used both at critical points in my recovery, with remarkable results. But true recovery requires probing the depths of what shaped you, how you adapted to it, and how those adaptations are now serving you (or not, as in my case). This also takes time. The biggest mistake of all is to believe you are ‘cured’ by a few months on a drug or a handful of therapy sessions, when in fact you are not even halfway there.” (399)

“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 doing.” (407)

Closing paragraph: “People get old when they stop thinking about the future. If you want to find someone’s true age, listen to them. If they talk about the past and they talk about all the things that happened that they did, they’ve gotten old. If they think about their dreams, their aspirations, what they’re still looking forward to—they’re young. Here’s to staying young, even as we grow older.” (411)

–> A focus on Future Ventures!