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Kindle Notes & Highlights
by
Mark Hyman
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October 19 - November 8, 2024
I’m not afraid of death, but I’m in no hurry to die. I have so much I want to do first. —STEPHEN HAWKING
there is a fundamental question you need to answer for yourself before diving into the revolutionary science that can extend both your health span (how many years you live in great health) and your life span (how many years you actually live). What is your why? What matters to you? Why might you want to live to be 100, or even 150 or 200—
what if we start approaching aging as a disease, and a treatable one at that?
The flaw in our approach to treating disease is that we think all diseases of aging—from heart disease to cancer, dementia, diabetes, and more—are different and that we need to find different cures for each one. However, the truth is that largely, they are just manifestations of the same underlying changes in biology that occur with aging and are highly influenced and modifiable by our lifestyle and environment washing over our genes.
We have four key nutrient-sensing systems that work together, with overlapping redundancies designed to beautifully protect us from disease and abnormal aging: insulin and insulin signaling, mTOR, AMPK, and sirtuins. Most of the dietary and lifestyle strategies that prevent disease, promote health, and extend life work through these nutrient-sensing systems.
The most important thing you can do for healthy aging is to balance your blood sugar and keep your insulin levels low and your cells insulin-sensitive, which means eating a low-sugar, low-starch diet with plenty of good-quality fats and protein, and a boatload of phytochemical- and fiber-rich fruits and vegetables.
Cycling periods of fasting or caloric restriction (which silences mTOR) with periods of adequate high-quality protein (which activates mTOR) to maintain and build new muscle is a powerful strategy for healthy aging.
There are certain phytonutrients that mimic a condition of beneficial stress called hormesis (discussed in Chapter 7), which can activate autophagy too. These include the polyphenols in coffee, oleuropein in extra virgin olive oil, resveratrol in red grape skin, catechins in green tea, turmeric, berberine, and a gut metabolite from phytochemicals in pomegranate called urolithin A.
The elegant nutrient-sensing systems in our body are listening for signals of scarcity or abundance, and through a whole cascade of biochemical reactions, they adapt to what’s needed in the moment. The key to health and longevity is balance: activating these pathways enough to rebuild and heal and grow but not too much to cause damage.
Many plant compounds have been found to activate AMPK and may result in longevity benefits similar to those of metformin, including areca nut, saffron, berberine from goldenseal, aloe, resveratrol, ginseng, reishi, hot peppers, artemisia, black cumin seed, bitter melon, tangerines, chlorogenic acid from coffee, and capsaicin from peppers.
studies found that resveratrol from red grape skin activates the sirtuin pathway.15 But remember, the dose was the equivalent of 1,500 bottles of red wine. Enjoy a glass of red wine occasionally, but don’t expect it to extend your life! Other beneficial compounds are proanthocyanidins, found in berries; quercetin, found in onions; curcumin, from turmeric; catechins, from green tea; persimmon; kaempferol, found in cruciferous vegetables; oligonol, from lychee fruit; butein, found in the Chinese lacquer tree and many flowering plants; and many compounds, like paeonol, used in traditional Chinese
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Regular aerobic exercise also activates sirtuins. In fact, many of exercise’s known benefits for health and longevity are due to its action on the sirtuin pathway. Exercise also stimulates a key enzyme called NAMPT, which is needed to produce more NAD+.
Supplementation of NAD+ and NAD+ precursors NR and NMN have been able to restore youthful levels, reversing age-related pathology and extending life. It is something I take every day, along with many other top aging researchers. NAD+ (and precursors NR and NMN) may be one of the most powerful discoveries in healthy life extension—it may be as close to the fountain of youth as we can get.
Senolytics include fisetin, from strawberries, persimmons, apples, cucumbers, and onions; luteolin, found in carrots, broccoli, artichokes, onions, chrysanthemum flowers, cabbages, and apple skins; quercetin, found in apples, grapes, berries, broccoli, citrus fruits, and cherries; curcumin, found in turmeric; and piperlongumine, an extract of goldenrod and an alkaloid found in long peppers.
The best way to clean up and rejuvenate old mitochondria is to eat a whole foods low-starch-and-sugar, good-fat, microbiome-supporting, polyphenol-rich diet, practice intermittent fasting or caloric restriction, and incorporate hormesis (good stress) routines like cold plunges or showers, aerobic exercise, strength training, and a few key supplements.
The hunter-gatherers had none of our modern chronic diseases, while their cousins had them all. The difference? Fiber.
Many of the advances in longevity science, such as calorie restriction; time-restricted eating; fasting; exercise; NAD+ therapy, rapamycin, metformin, and various phytochemicals such as resveratrol, fisetin, and quercetin; cold therapy; red-light therapy; hyperbaric oxygen; ozone; and hypoxia or low oxygen states (which we will cover in Chapter 10), work through improving the number and function of your mitochondria, no matter how old they are.
The foundational principles of eating for health and longevity are not in dispute and can be summarized in Michael Pollan’s pithy aphorism, “Eat food. Not too much. Mostly plants.”
How do you feed the good bugs? They munch down on the fibers in our food. These are called prebiotics. Fiber-rich foods help keep the garden healthy: vegetables, fruits, nuts, seeds, whole grains, and beans. Certain foods have high levels of prebiotic fibers, including avocados, artichokes, asparagus, berries, peas, chia seeds, and pistachios. Probiotic-rich foods, including traditional fermented foods like sauerkraut, pickles, tempeh, miso, natto, and kimchi, also help support a healthy gut.
Akkermansia muciniphila, loves cranberry, pomegranate, and green tea.
Your gut needs other nutrients, too, to function well and heal: zinc, omega-3 fats, vitamin A, and glutamine. Foods with collagen such as bone broth, and kudzu, a Japanese root, also help your microbiome.
Extra virgin olive oil, a nice green color, contains oleocanthal, which has anti-inflammatory properties similar to ibuprofen without all its side effects. Spices like turmeric, ginger, and rosemary are anti-inflammatory powerhouses. Meat cooked with spices neutralizes any potential inflammation.7 Mushrooms regulate the immune system and contain anticancer compounds. And foods rich in vitamin C, zinc, selenium, and vitamin D strengthen your immunity and slow down inflammation.
Foods such as blueberries, pomegranate seeds, grass-fed beef and butter, broccoli, sardines, extra virgin olive oil, avocados, and almonds are great sources of fat and phytonutrients that supercharge your mitochondria.
The food group that best boosts liver detox pathways is the cruciferous vegetable family (broccoli, collards, kale, cabbage, Brussels sprouts), which contains sulfur compounds that enhance the production of glutathione, the most powerful antioxidant in your body. Garlic and onions also provide the sulfur needed for detoxification. The liver also needs adequate levels of B1, B2, B3, B6, B12, folate, manganese, magnesium, zinc, and selenium found in animal protein, seafood, nuts, seeds, and green vegetables to facilitate all the chemical reactions needed for detoxification. The rich array of
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Green tea is a super detoxifier,
Rosemary, ginger, cilantro, dandelion greens, parsley, lemon peel, watercress, burdock root, and artichokes are all powerful detoxifying foods that should be consumed on a regular basis.
Women benefit from including in their diet non-GMO traditional soy foods such as miso, natto, tempeh, and tofu; flaxseeds; cruciferous vegetables; and lots of fiber.
Adding foods rich in zinc (meat, seeds, nuts), selenium (sardines and Brazil nuts), vitamin D (egg yolks, porcini mushrooms, and herring), and iodine (seaweed and fish) can help optimize thyroid function.
Your body needs the amino acid arginine to produce nitric oxide, and the best food sources are pumpkin seeds, sesame seeds, walnuts, almonds, turkey breast, soybeans, and seaweed. Omega-3 fats from wild fish also help improve endothelial function (the function of the lining of the blood vessels) and prevent dangerous clotting.16 The heart-healthy benefits of olive oil come from the effect of polyphenols on endothelial function and reducing blood vessel inflammation.
many foods help improve lymphatic function, including green leafy vegetables, ground flaxseeds, chia seeds, avocados, garlic, nuts, seaweed, citrus fruits, and cranberries. Phytochemically rich herbs can also help, like echinacea, astragalus, cilantro, and parsley.
The best type of protein to build muscle is other muscle: animal protein.
The only thing that all nutrition scientists agree on is that health and longevity are directly tied to the number of fruits and vegetables in your diet
the polyamine spermidine, found in human sperm cells but also in mushrooms, aged cheese, and soybeans (notably in natto, a fermented soybean preparation) and available as a dietary supplement, extends life span in mice and people.
Himalayan Tartary buckwheat,
Resveratrol prevents leaky gut and reverses dysbiosis. Quercetin and ginseng do the same thing.
Another promising “longevity molecule,” urolithin A, is produced when certain gut bacteria (often depleted in modern humans) are exposed to the phytochemicals in pomegranate, berries, and walnuts.
If you are doing weight training and aerobic exercise, you may need 105 to 140 grams a day
The per-meal anabolic threshold (the amount of protein that triggers muscle building) of dietary protein and amino acid intake is higher in older individuals (i.e., 25 to 40 g protein per meal, containing about 2.5 to 2.8 g leucine) compared to that in young adults. If you eat less than that, the protein is used for calories and energy rather than for making muscle.
The average person needs 25 to 40 grams of high-quality protein per meal, depending on age, activity level, and illness. That’s a lot more protein than many get. 2. The best timing of protein intake is within an hour or two after exercise.
Whey protein is the best source of easily absorbable high-quality protein that’s high in leucine and other key amino acids for muscle building. I like regeneratively raised or organic goat whey. It is better tolerated by most. A protein shake after a workout is a powerful muscle-building strategy.
if you eat more than you need, the excess protein is simply used as calories and can be turned into sugar by your body (via something call gluconeogenesis).
The best rule of thumb is to eat a palm-sized piece of animal protein (or the equivalent in grams of whey protein or plant proteins) at every meal.
Bottom line: Eat high-quality protein daily to meet your needs based on age, health concerns, and activity level, ideally 1.2 to 1.5 grams per kilogram per day if you are active (which you should be). Combine plant and animal proteins to improve overall protein quality. Add branched-chain amino acids and creatine for building muscle. Take a 12- to 16-hour break from eating each day (practice time-restricted eating) to allow mTOR to quiet down and induce autophagy. Add exercise and strength training, and voilà, you have a muscle-building longevity plan.
Walking is great, but more vigorous activity for about 75 to 150 minutes a week is better. Add in three to four days of strength training with bands, weights, or body-weight exercises, including squats, push-ups, shoulder presses, chest presses, and planks.
Having a sense of purpose is associated with overall well-being, improved physical and cognitive health, reduced depressive symptoms, and slower aging.
Meaning makes a great many things endurable—perhaps everything. Through the creation of meaning… a new cosmos arises. —C. G. JUNG
Dr. Robert Butler, the first director of the National Institute on Aging, performed a study that looked at having a sense of purpose and life expectancy. He found that people who have a clear sense of purpose, a reason to get up in the morning, lived up to seven years longer than those who didn’t have a clear purpose. In another study of 7,000 adults, published in the Journal of the American Medical Association, those who had the lowest life purpose scores were twice as likely to die as those with the highest scores.
The world of biohacking (essentially the layperson’s version of functional medicine) incorporates many hormetic strategies: Time-restricted eating and fasting High-intensity interval training and strength training Cold plunges and saunas Breath work, hypoxia (low oxygen states) Hyperbaric oxygen therapy Ozone therapy Light therapy Phytochemicals
the only thing that predictably extended life in animal models was eating a third fewer calories.
Certain plant compounds may mimic caloric restriction and lead to xenohormesis, activating autophagy. Some of these include the polyphenols in coffee; oleuropein, found in extra virgin olive oil; resveratrol, found in red grape skin and Japanese knotweed; sirtuin activating compounds, or STACs, such as fisetin from strawberries; spermidine (yes, it comes from where you think!); catechins, found in green tea; curcumin, found in turmeric; berberine; and a gut metabolite of pomegranate called urolithin A.
