How Not to Age — Presentation

So, without further ado, may I present the founder and director of NutritionFacts.org, Dr. Michael Greger. There may be no such thing as dying from old age. From a study of more than 42,000 consecutive autopsies, centenarians— those who live to be a hundred— were found to have succumbed-to-disease in a hundred percent of the cases. Though most were perceived, even by their physicians, to have been healthy just prior to death, not one, “died, of old age.” They died from disease, most commonly, heart disease. If aging kills via diseases, why wasn’t my book How Not to Die all

the longevity book anyone needs? In it, I ran through preventing, arresting, or reversing each of our top 15 killers— starting with heart disease, not only the #1 killer of centenarians, but of men and women across the board and projected to remain that way in the decades to come. But is it really? Because the single greatest risk factor for most of our killer diseases is how old you are, one could argue that the leading cause of death is actually aging. The rate of death increases exponentially for age-related diseases, such as heart disease, cancer, stroke, dementia. So

yes, within the same age bracket, having a high cholesterol can increase your risk of heart disease up to 20-fold, but an 80-year-old may have five hundred times the risk of having a heart attack compared to a twenty-year-old. Now, the reason we focus on things like cholesterol is because it’s a modifiable risk factor, but what if the rate of aging was modifiable too? Instead of our current piecemeal approach of focusing on individual diseases, what about slowing down the aging process itself? When I was a nerdy little kid, I wanted to cure cancer when I grew up.

But even if all forms of cancer were eliminated, the average life expectancy in the U.S. would only go up about three years. Why? Because dodging cancer would just mean delaying death from a heart attack or stroke. If one age-related ailment doesn’t get us, another will. So, rather than playing “whack-a-mole” by tackling each disease separately, slowing the rate of aging could potentially address all these issues simultaneously. Imagine if there were an intervention that didn’t just reduce your risk of the leading killers, but also arthritis, osteoporosis, sensory impairments. Because risks tend to double every seven years— like

if the average 65-year-old had the health of a 58-year-old? Slowing aging by even just seven years could cut everyone’s risk of death, frailty, and disability in half. That’s why I wrote How Not to Age. The problem is that the anti-aging field is said to be a “fertile ground for cons, scams, and get-rich- quick schemes.” As a former president of the Gerontological Society wrote, there have been “few subjects which have been more misleading to the uncritical and more profitable to the unscrupulous.” Not only does the popular literature on the subject harbor a “huge amount of misinformation,”

but most age-researching scientists widely known to the public are said to be “unscrupulous purveyors of useless nostrums,” according to the Editor-in-Chief of a leading gerontology journal. When it comes to something as life-and-death important as to what to feed ourselves and our families, we should rely not on anecdote, but on evidence. That’s why I cite everything to the teeth. How Not to Die, had about 2,000 citations. How Not to Diet, 5,000 citations. How Not to Age ended up with 13,000 citations, all of which I have hyperlinked for you online to access all the original sources. So,

you can download the studies and read them all yourself. My aim was to cover every possible angle for developing the optimal diet and lifestyle, for the longest, healthiest lifespan— based on the best available balance of evidence. My inspiration for writing the book was a consensus document, “Interventions to Slow Aging in Humans”, compiled by the top researchers in the anti-aging field (the likes of Drs. Longo, Sinclair, Fontana). They were brought together to identify the most promising strategies to combat aging. They identified a list of “essential pathways,” for example, drugs that can block the hormone IGF-1, or

drugs to block the pro-aging enzyme TOR. But I realized as I looked at this: Wait, every single one of these pathways could be regulated through diet. That became the first section of the book. The term “antiaging” has been much abused in popular culture, attached to all manner of unproven products and procedures, whereas the term should really be reserved for things that can delay or reverse aging by targeting one of the established aging mechanisms, the so-called Hallmarks of Aging, the common denominators of the aging process like, for example, the buildup of misfolded proteins that can be

disposed of through autophagy. See, at any given time, most of our cells are producing and assembling more than 10,000 distinct proteins, each of which can become misfolded or damaged at any time and require a cleanup in aisle three. But during times of nutrient excess, our body figures why bother? We can just toss it in the corner and make another. Having evolved in a context of scarcity, our body expects to fall on hard times any day now and can put off spring cleaning until then. But these days, these lean times hardly ever come; so, our cells

just end up continually hoarding junk. That’s where autophagy comes from, from the Greek words for “self-eating.” It’s a housekeeping process by which defective cellular components are broken down and scrapped for spare parts. This doubles as both salvage operation and quality control, clearing out some of the damaged debris implicated in the aging process, while renewing our cells in a sort of cellular reset. As one review put it, “The janitor is the undercover boss.” Our ancient ancestors often went for several days without food; so, autophagy was constantly being switched on. But these days, our cells no longer

need to clean out the corners for sustenance. And so, the tainted heaps just pile higher and higher, which isn’t good, because autophagy is essential for lifespan extension. It’s not only necessary, but sometimes sufficient for increasing longevity. Self-digestion for lifespan extension. Boosting autophagy alone can boost lifespan, at least in mice, by an average of 12 percent, and it also boosts healthspan. Unfortunately, our bodies’ ability to take-out-the-trash declines with age, leading to this vicious cycle. Garbage builds up, accelerating aging, which leads to more garbage buildup. No wonder the drug industry is so eager to pharmacologically modulate autophagy

to combat aging— but we can do it naturally. One way is through fasting. Unfortunately, autophagy doesn’t really maximally ramp up until after a day or two of fasting, which may be too long to do it unsupervised. Fasting more than 24 hours should probably only be done under medical supervision, ideally in a live-in clinic. In other words, don’t try this at home. This is not just legalistic mumbo-jumbo. For example, normally, your kidneys dive into sodium conservation mode, but should that response break down, you could rapidly develop an electrolyte abnormality that might only manifest with non-specific symptoms

like fatigue or dizziness, which could be easily dismissed, until it’s too late. Thankfully, there’s another way to activate autophagy. You can fast or go fast. Exercise induces autophagy. As one of the researchers said, “I’ve always known exercise was good for you, but when we found that it increases autophagy, I finally got a treadmill.” You have to do enough, though. Autophagy is activated after 60 minutes of moderate intensity exercise, but only twenty minutes fails to move the needle. What about diet? Any foods to avoid? In 2021, we found out acrylamide can inhibit autophagy, at least in

cells in a petri dish. Acrylamide is a toxin concentrated in French fries and potato chips that’s formed during the frying process. The fact that high acrylamide exposure is associated with as much as double the risk of premature death would be consistent with an anti-autophagy effect, though diminished lifespans among eaters of fatty, salty snacks isn’t exactly a revelation. You can’t know if it's cause and effect, until you… put it to the test— very nice! Before being asked to eat a bag of potato chips every day for a month, study subjects were given weeks of boiled potatoes

mixed with the same amount of fat and salt as the chips. Compared with the fatty salty boiled potatoes, their C-reactive protein levels shot up 50 percent on the chips, suggesting “chronic ingestion of acrylamide-containing products induces a proinflammatory state.” However, deep frying causes the formation of all manner of “undesired food-borne toxicants;” so, we can’t be sure it was the acrylamide. As one of the earliest geriatric medicine textbooks presciently concluded back in 1849, “frying…is an abomination.” If you just must have your French fry fix, air-frying produces about 90 percent less acrylamide. Anything that can help? Starving yourself

“generates discomfort,” but there is something that activates autophagy that many people find comforting: coffee. At a human- equivalent dose, both regular and decaf rapidly induce autophagy within hours— in mice, and coffee can extend the lifespans of some rats, but what about people? In humans, we only have observational research, but to date about 20 studies have followed more than 10 million people over time, and those drinking 3 cups (720 ml) of coffee a day had 13 percent lower risk of dying from all causes put together. And decaf appears to be just as protective; so, it’s not

the caffeine. Coffee contains more than a thousand bioactive compounds. The polyphenol chlorogenic acid is the most abundant antioxidant in coffee; so, researchers started there, and indeed, was found to enhance autophagy in human cells. More than a hundred coffees have been tested, and chlorogenic acid levels vary by more than 30-fold. Interestingly, the major contributor to this wide range is Starbucks, with its extremely low chlorogenic acid content, thought to be because they roast their beans so dark that they destroy it. Freeze-drying is okay, and brewed has more than espresso. Paper filtered is the best, because it traps

the cholesterol- raising compounds in coffee, perhaps explaining why those drinking filtered coffee had even lower mortality rates than those drinking unfiltered coffee. Any food components that activate autophagy? Spermidine, the longevity elixir, spermidine. Don’t be put off by the name. Spermidine and its byproduct spermine are actually found throughout the body. When it was later independently discovered in the brain and the muscles, they called it neuridine and musculamine until they found out it was all the same compound, and so, naming rights defaulted to the less palatable original. Our body can make it from scratch, but we can

also boost levels by eating spermidine-rich foods, which is good news because our spermidine levels tend to decline with age, dropping more than half by the time we reach our 50s. This decline is seen across the biological spectrum with one remarkable exception, naked mole rats, also known by their more cuddly nickname: sand puppy, considered to be a “non-aging mammal” without any visible signs of aging and almost no decline in physiological function over decades, or typical signs of aging, like loss of fertility or muscle mass. Perhaps in part because they are able to maintain their high levels

of spermidine, something you also see in human centenarians. To prove cause and effect, extra spermidine was fed to animals and “Induction of Autophagy by Spermidine Promotes Longevity,” increasing the lifespans of mice, for example, by as much as 25 percent. In a database of more than a thousand life-extending compounds, among the small subset with the fewest side effects, spermidine has the largest documented lifespan extension. Longevity can be improved even when started late in life, kind of the human equivalent of changing your diet when you’re already in your fifties. Anti-aging effects were found in the heart and

kidneys, rejuvenating immune function, delaying brain aging, and improving cognitive function. Yeah, but that was in animals like fruit flies and mice. I mean who cares if spermidine cures flies of senior moments. What about in people? Hundreds of men and women in their 40s through 80s were followed for twenty years, and after looking at 146 different components of their diets, the single most predictive of longevity was spermidine. How much spermidine? Higher spermidine intake is linked to lower mortality. Those who consumed the most spermidine had a reduced risk of death from all major causes, which is what

we’d expect from an anti-aging compound. Critically, this survival advantage persisted even after controlling for dietary excellence, meaning that it wasn’t just because they were eating healthier foods in general, but rather spermidine- rich foods in particular. How big of an effect are we talking? The reduction in mortality risk between getting more than 12 mg of spermidine a day compared to getting less than 9 was as if those eating more spermidine were 5.7 years younger. It’s as if by eating more of certain foods, they were effectively able to turn back the clock nearly 6 years. The findings

were so extraordinary, the researchers sought to replicate their results in a whole new set of individuals and, indeed, arrived at the same conclusion. This led some to propose that spermidine may be an anti-aging vitamin. When we’re younger, we seem to be able to make enough, but as we get older, we may need to start ensuring we’re getting enough in our diet to maintain autophagy into old age. Well, if spermidine is going to be considered an anti-aging vitamin, where is that vitamin found? Beans are said to have the highest natural amounts, but I compiled a list

of the top spermidine sources, and pig pancreas beat out bean burritos for the bronze. This is virtually every food averaging at least 2 mg of spermidine per serving, with a fermented whole soy food called tempeh leading the list, along with plain white mushrooms. While some have suggested the genetic engineering of spermidine-rich crops, there are already a plethora of naturally spermidine-rich foods. As a certified dark green leafy snob, I was begrudgingly impressed to see lettuce score so high, though lettuce is so light, a 100-gram serving would be about 3 cups, but even the spermidine in little

side salads could really add up. In the book, I spend a lot of time going through the list, but the single most concentrated source is wheat germ, with 2.5 mg of spermidine in just the 7 grams in a tablespoon. It’s also the cheapest source, costing as little as two cents per milligram. You can’t get a lot of pancreas for two cents. Does wheat germ actually do anything? Let’s randomize people to some dinner rolls and find out. A randomized, double-blind pilot in which older individuals were secretly slipped some spermidine in the form of wheat germ baked

into bread rolls vs placebo rolls with wheat bran instead. And, those with mild dementia improved way beyond all available antidementia drug treatments so far. Admittedly, that’s not saying much, but what’s the harm of sprinkling a little wheat germ on your food? The latest Alzheimer's drugs don’t appear to work at all. All you get for your 56,000 dollars is a dramatically increased risk of swelling or bleeding into your brain. When the FDA approved it anyway, the head of the American Geriatrics Society replied, “My head just exploded.” (Maybe they just got slipped a dose of the drug).

Anyway, lots of other clinical spermidine studies, but just to wrap up this section, autophagy is considered the “primary system for cleaning the body” from the inside out. And, we can boost autophagy with aerobic exercise, skipping fries and chips, drinking coffee, and eating specific foods to reach a target of 20 mg of spermidine a day. I offer similar diet and lifestyle takeaways for each of the other 10 anti-aging pathways, but don’t have time to touch on them, because there’s still three other major sections of the book. Part Two focuses on the diets and lifestyles of the

healthiest and longest-lived populations around the world. The odds of living to a hundred have risen from approximately 1 in 20 million to as high as 1 in 50. Why do some make it and others not? It’s not just a matter of picking better parents. Studies following identical twins suggest that only about 25 percent of the variation in lifespan is explained by genetics. So, what can we do for the majority over which we may have some control? The media loves stories of hard-living centenarians who attribute their longevity to some combination of lard, vodka, and favorite brand

of cigarette, but how do the oldest and healthiest really eat and live? That’s what we have the blue zones for, areas of exceptional longevity around the world, where there may be ten times the rate of those reaching those triple digits. (Named for the color a demographer used in a global “heat map” of mortality around the world.) What lessons can we learn? The Blue Zones organization distilled findings from more than 150 dietary surveys from the world’s longest-living people to create a set of ten food guidelines. The foundation of the Blue Zones Food Guidelines, is making your

diet at least 95 percent plant-based, avoiding highly processed foods, emphasizing beans as the healthiest source of protein, water as the best beverage, and nuts as the healthiest snack. That’s the foundation. The final five guidelines are to “Go easy on fish,” “Eliminate eggs, “Slash sugar,” “Reduce dairy,” and “Retreat from meat,” noting that blue zones centenarians only eat about two ounces (57 g) of meat or less about five times a month. Historically, there’ve been five recognized blue zones, but only one survives and thrives to this day, the red, white, and blue zone: the Seventh-Day Adventists in Loma

Linda, California, with perhaps the longest life expectancy of any formally studied population in history. There are a number of shared Blue Zone lifestyle characteristics: family coherence, avoiding smoking, daily exercise, social engagement, but plant-based nutrition appears to be the principal component, alone accounting for about half the difference in lifespan. No surprise, since the number one risk factor for death in the United States is the American diet. So, unsafe sex is bad. Sedentary lifestyle? Bad. Alcohol and drugs— especially tobacco. Bad. But cigarettes only kill about a half million Americans every year, whereas our diet kills many more.

We are what we eat. Which is good news, because it means we have the power. Changing from a more typical diet to a more optimized diet starting at age twenty would be expected to increase the lifespan of women by about eleven years and men by thirteen years. The largest life expectancy gain would be made by eating more legumes— in other words, more beans, split peas, chickpeas, and lentils. So, if there was one thing we could eat: Legumes for longevity. Hummus for health! Then, comes whole grains and nuts, and eating less meat. Now, for the few

of you who aren’t twenty anymore, not to worry. Starting to eat healthier at age sixty, could still mean adding eight or nine more years to your lifespan. Even starting as late as age eighty could add years. Changing your health destiny can start tomorrow morning at breakfast. And it doesn’t take much. The NIH-AARP study is the largest forward-looking study on diet and health in history. Based on its six million person-years of observation, replacing just three percent of daily caloric intake from animal protein with plant protein was associated with a ten percent decreased risk of overall mortality

in both men and women. Just swapping three percent! Of all the animal protein sources, eggs were found to be the worst. Swapping in three percent of plant protein for egg protein was associated with twice the benefit, twenty percent lower mortality for swapping in a few British beans for breakfast instead. Harvard researchers found that when it comes to premature death, processed meat was the worst, followed by eggs. In essence, they found that tuna salad may be better than egg salad or a BLT, but a bean burrito beat out the bunch. When it came to death from

all causes put together, plant protein beat out every type of animal protein— including dairy, fish, and chicken. A three percent swap from chicken to chickpeas, or fish to falafel was linked to a six percent decreased risk of premature death. But does eating healthy actually slow down aging? Randomize hundreds of women to a diet centered around healthy plant foods, or exercise, or neither, and though the physical activity failed, those in the plant-based dietary intervention group had a significant slowing of biological aging. Of course, it isn’t just about adding years to your life, but life to your

years. An unhealthy aging index was devised to measure functional impairments, vitality, mental health, physical health. Substituting even just one percent of calories from plant protein for animal protein appeared to lead to significantly less deficit accumulation. And substituting five percent may reduce the risk of dying from the greatest deficit, dementia. That may help explain why those who don’t eat any meat at all may be up to three times less likely to become demented. But again, it’s not all-or-nothing. In fact, the worst thing about humanity’s diet is neither animal nor vegetable, but mineral: sodium. Here are the

top five fatal flaws of our diet. Millions of deaths may be attributable every year to not getting enough whole grains, not eating enough fruit, not enough nuts and seeds, not enough vegetables. But the single deadliest ingredient in humanity’s diet is something we get too much of: and that’s salt, our number one dietary risk factor for death. A recent whopping study, for example, of more than a half million people found that those who salted their food at the table at age fifty appeared to have about a two-year lower life expectancy compared to those that didn’t. So,

just swapping out the salt shaker for some salt- free seasoning or salt substitutes could potentially add years to your life. How do we know it’s cause and effect? Five kitchens at a veterans’ retirement home were randomized into two groups for a few years, offering meals salted either with regular salt or, unbeknownst to them, a 50/50 blend of regular salt, sodium chloride, with a salt substitute like these, potassium chloride. The kind of salt was the only difference between the meals, and cardiovascular disease death rates plummeted by 40 percent in the folks getting the reduced sodium blend.

The new difference in life expectancy between the two groups at age seventy was equivalent to that which would have occurred naturally in 14 years, meaning simply switching to even half potassium salt— for which you wouldn’t even be able to taste the difference of— appeared to effectively make people more than a decade younger when it came to the risk of premature death. What do the likes of the Salt Institute have to say about public health recommendations to reduce sodium intake? In testimony before a Congressional committee, the presumption that healthier diets would cut healthcare costs was challenged.

“Indeed,” one processed food defender testified, “healthcare expenditures increase if the lifespan is prolonged.” If people eat healthier and live longer, it could be more expensive, noting that if tobacco were banned, the increase in expected lifespan would, “increase the cost of care of old people.” Think how expensive it would be if people started taking care of themselves and didn’t, conveniently, die on time. Ultra-processed foods, often packed with added salt, sugar, and fat, consistently account for more than 50 percent of our dietary caloric intake. More than half of our diet is junk. Not surprisingly, those foods are

associated with a greater risk of dying prematurely. So, just cutting back on animal foods isn’t enough. Healthy plant-based diets are associated with a significantly lower risk of dying, but unhealthy plant- based diets are not. In the Harvard cohorts, the more you minimize meat, eggs, and dairy, the lower your risk of death falls, but that’s only if you’re eating healthy plant foods. If you, instead, just pile on the junk, like chips and soda, you can increase your risk of death overall— even if animal product consumption remains low. Same in the Million Veteran Program study: Healthy plant

foods, reduced their risk of death. But if your idea of a plant- based diet is fries and a Coke, you’re not doing your body any favors. Same with the risk of cognitive impairment. Only healthy plant foods reduce risk. The same with dementia and depression. The same with frailty. Healthy plant foods good; plant-based junk bad. That’s why Cornell Professor Emeritus of Biochemistry, T. Colin Campbell, coined the term whole food, plant-based diet. As a physician, terms like vegetarian or vegan just tell me what you don’t eat. I mean, do you actually eat vegetables? Professor Campbell’s physician son

and daughter-in-law tried putting a group of vegetarians and vegans on a whole food, plant-based diet. In eight weeks, they lost ten pounds, dropped their LDL cholesterol 15 points. In other words, vegans may benefit from eating a little more plant-based, too. Now, meat is a problem. In terms of lifespan, eating a burger may cut one’s life as short as smoking two cigarettes. So, if it wouldn’t even occur to us to light up before- and-after lunch, maybe we should choose the bean burrito instead. There are certainly ways to make meat safer, though. For example, one of the

ways whole food, plant-based diets can help is by reducing the load of gerontotoxins, age-accelerating toxins, such as advanced glycation end-products, also known as glycotoxins, or AGEs, an acronym intentionally chosen to emphasize their toxic role in age-related disease. AGEs occur naturally in animals, but dry cooking methods can generate 10 to 100 times more. When muscle cells rupture under dry heat, highly reactive compounds combine with blood and body sugars to form AGEs within the meat. So, even without cutting down on meat, you can significantly cut down on glycotoxin intake, just by switching up cooking methods. The safest

ways of cooking meat are moist methods, such as boiling, poaching, steaming, stewing. Check out what happens when people are randomized to a meal of fried or broiled chicken breast and veggies— or the same meal with the same ingredients— including the oil— but with steamed or boiled chicken breast instead? That single high AGE meal with the fried or broiled breast induced a profound impairment of artery function within hours. The steamed chicken still impaired artery function, but not as much as the fried or broiled. So, we can eat an “age less” diet by switching to moist methods,

for example, but dietary approaches are said to have “zero commercial value” and hey, stewed chicken may not be as tasty; so, why not just take a drug to block AGE absorption every time we eat? It does lower your blood levels of AGEs. It’s just activated charcoal, like when people are poisoned or for drug overdoses. I’m sure our AGEs would also go down if we chased our chicken with a little ipecac, too. What about fish? Unfortunately, our oceans have essentially become humanity’s sewer. Everything eventually flows into the sea; so, the consumption of contaminated seafood has become

the main route of human exposure to chemical pollutants. Yes, a variety of foods are affected, but the number one source of DDT? Fish. The number one source of PCBs? Fish. Salmon is the worst when it comes to PCBs, followed by canned tuna. Salmon also has the highest levels of dioxin-like compounds. So, on the one hand, fish has long been viewed as a healthy dietary component because of those long-chain-omega-3’s, but on the other hand, we’re so polluting our world that we’re now seeing heavy metals, pesticides, flame retardants in fish, forever chemicals, which may explain why, despite

their omega-3’s, there’s been a failure to consistently observe beneficial effects of fish consumption. So, if we had a time machine to go back before the industrial revolution, that would be one thing, but now, we have studies like this, where mice fed commercially available farmed salmon fillets with common levels of persistent organic pollutants were found to develop insulin resistance, glucose intolerance, abdominal obesity, fatty liver, chronic low-grade inflammation. So, even just background levels of pollutants that might be presumed to be safe could completely counteract the potential benefits of omega-3s, in particular, leading to metabolic issues. For mercury,

it’s more about brain health. Hundreds of thousands of babies born with brain damage every year, seemingly as a consequence of their mothers consuming mercury-contaminated fish during pregnancy, with the resulting loss of intelligence estimated to cause billions of dollars of lost productivity every year. In the aging literature, there are cases like this: a man with progressive memory loss tentatively diagnosed with Alzheimer’s dementia. His friends and family assumed he was nearing the end of his life. But a detailed history revealed that he had consumed swordfish once or twice a week. When the fish was removed from his

diet, his mercury levels fell, and his memory bounced back. No more dementia. So, it seemed he didn’t have Alzheimer’s after all, but rather mercury poisoning from a handful of monthly meals of contaminated fish. You can see the same remarkable reversals with hair loss. Here’s a common story: a perimenopausal woman seeks help for hair loss. Blood tests indicate elevated mercury levels. And no wonder, because she had a diet high in tuna. But within two months of stopping fish, her hair started to grow back, and eventually her hair regrew completely. So, doctors should consider screening for mercury

toxicity when they see hair loss, since there’s something we can do about it. Instructing patients to reduce fish intake could offer relief of symptoms and uncover dietary habits that may be a source of heavy-metal-induced hair loss. (Though, admittedly, sometimes heavy metal can lead to too much hair.) What about alcohol? That’s from plants! Sorry to be Dr. Buzzkill, but alcohol appears to be humanity’s 7th leading cause of death and disability. The safest level of drinking is none. But wait a second, what about the famous J curve, where light to moderate drinkers appear to have lower mortality

rates than the teetotalers at zero drinks a day? This, may just be an artifact of the systemic misclassification of former drinkers as lifelong abstainers. This leads to the so-called “sick-quitter” effect, where the reason a person may be a nondrinker is because drinking made them sick, thereby making current drinkers look good in comparison. It’s the same reason studies can find higher mortality among those who quit smoking compared to those who continue to smoke. It’s not that abstention led to poor health, but poor health rather led to abstention. When researchers went back and controlled for the error

of misclassifying former drinkers, the J curve disappeared. No more apparent benefit to moderate drinking. In other words, compared to true abstainers, the more alcohol, the more disease, with no apparent protection at low levels of consumption. Even red wine? Unfortunately, interventional trials show that wine can cause inflammation within hours of consumption, both red and white— significantly more than just like drinking sugar water, and you get a surge of fat in your bloodstream that you don’t get drinking “dealcoholized red wine” (the same wine with the alcohol taken out). What about just taking supplements of the red wine

compound resveratrol? Oh, you mean the supplement found to nearly triple the loss of brain tissue compared to placebo? No, thank you. The healthiest beverages are probably water and tea. Increasing tea consumption three cups (720 ml) a day may decrease the risk of premature death from all causes by 24 percent. This applied to both green and black tea, though green may have a slight advantage. Part of this protection may be a lower risk of dying of pneumonia. There have been five randomized, controlled trials showing those randomized to green tea are about a third less likely to

come down with the flu, for example. Within just one hour of drinking a single cup (200 ml) of green tea, we can significantly cut down on the rate of DNA damage in our cells, because green tea significantly boosts the activity of a DNA repair enzyme in our body that can fix DNA damage. And within a month, drinking two small daily cups (400 ml) of green tea can improve DNA resistance to free radical damage in the first place, indicating that green tea has significant genoprotective effects, or DNA protecting effects. Tons more about individual foods and beverages

in the book. But let’s move on to Part Three, where I get into the nitty gritty. What can we do to protect our bones, bowels, bladder, and circulation? Our hair, hearing, and hormone balance? Immune function, joint health? Our minds and our muscles? Sex life and skin? Our teeth, vision, and finally, our dignity in death. Let me just share a few quick pearls. For example, did you know that 85 percent of bone-related fracture risk has nothing to do with your bone mineral density? That’s just been drilled into our heads by big pharma and a billion-dollar bone

density screening industry. Fractures are primarily due to falling, not osteoporosis. So, it’s the age-related muscle loss and impaired balance that may be breaking most of our bones— which is good news, because there’s something we can do something about it. Seven randomized controlled trials found that strength and balance training can cut fracture rates nearly in half— and that’s just during the trial. In the five years after this one-year study ended, those who had previously been randomized to the combined strength and balance group, suffered 74 percent fewer fractures. That’s far more effective than osteoporosis drugs like Fosamax

that can cause fractures— atypical femoral fractures, in as many as 1 in 300 users. They are called “atypical,” because they occur not after a fall or trauma but just during routine activities, like walking, twisting at the hip, or even just standing still. Thanks to the drug, your femur, your thigh bone, the biggest bone in your body— just cracks in half. Too cruel an irony from a drug that’s supposed to protect your bones. This is what it looks like on x-ray. Ouch! After bones, I talk about preserving your bowel function in chapter number two. Randomize constipated

diabetics to either cookies containing a tablespoon (20 g) a day of ground flaxseeds or flax-free placebo cookies for 12 weeks and not only does the flax improve constipation symptoms but resulted in an eight-pound weight loss over placebo, 25-point lower blood sugars, an astounding drop in hemoglobin A1c, and 17-point lower LDL cholesterol. All for about 10 cents a day of ground flaxseeds. For a head-to-head test between flaxseeds and psyllium, sold as Metamucil, a third cookie group was added with 10 grams of psyllium, and the flaxseed beat out the psyllium for constipation relief, weight, blood sugars, and

cholesterol— and, is about four times cheaper. Flaxseeds were also directly compared to the prescription laxative lactulose and worked better as well. Bladder function! The prevalence of overactive bladder syndrome increases with age, reaching about one in three. No wonder bladder-relaxing drugs are a multibillion-dollar industry, yet may only reduce bathroom breaks by a half a pee a day compared to placebo. But a quarter teaspoon (500 mg) a day of dried cranberry powder worked nearly four times better, about two fewer daily trips to the bathroom over placebo, and that’s without any of the drug’s side effects: dry mouth,

constipation, sedation, impaired cognition, rapid heartbeat, urinary retention, and the visual disturbances that lead almost two-thirds to stop taking the drugs, whereas cranberries are just tangy. Urinary incontinence is a common problem among older adults, particularly women, thanks to childbirth. Systemic menopausal hormone therapy like Premarin actually makes it worse, but local, vaginal estrogen may help. What works five times better than estrogen cream though? Kegel exercises, pelvic floor exercises, as I detail in the section “Jacked in the Box.” For men, urinary issues are more an enlarged prostate problem, having to get up multiple times at night, wee hours

of the night. Cranberries to the rescue there again. Even just an eighth of a teaspoon (250 mg) a day of powdered cranberries can significantly improve prostate symptoms. You can buy cranberry powder in bulk at a cost of less than a penny per day. What about saw palmetto, the most common herbal supplement used for prostate symptoms? Based on dozens of randomized, controlled trials involving nearly 5,000 men: no clinical benefits. But pumpkin seeds work. More than a thousand men with prostate symptoms were randomized to either about a tablespoon (15 g) a day of plain pumpkin seed kernels,

a proprietary pumpkin seed extract, or a placebo. The study was funded by the drug company that made the supplement, but the supplement totally flopped, while the pumpkin seeds themselves worked. Pumpkin seed oil was pitted against the leading drug for hair loss in women. A little less than a quarter teaspoon (1 ml) applied to the scalp once a day versus a dose of the drug, and they both worked, but the drug worked better. Rosemary oil, however, may be more closely matched. A hundred balding men were randomized to twice a day minoxidil like Rogaine versus a rosemary

lotion. It took six months, but significant comparable improvement in hair counts in both groups, with no significant difference between the two. The rosemary lotion appeared to work as well as the drug. If you want to give it a DIY try, you can premix about 10 drops of rosemary essential oil to each fluid ounce (30 ml) of your favorite lotion and rub a quarter teaspoon (1.23 ml) into your scalp twice a day. Cost-wise, that much rosemary oil would come out to be about a penny per week. Let’s move on from hair highlights to hormones. I touched

upon how menopausal hormone therapy can increase the risk of urinary incontinence, but that’s not all. If a thousand postmenopausal women take the standard hormone regimen for ten years, you’d not only expect 876 extra cases of urinary incontinence that they would not have got otherwise, but nine more cases of invasive breast cancer, eight more cases of heart disease, probably 22 more cases of dementia, 21 more cases of gallbladder disease, nine more strokes, and 21 more blood clots— though not a single partridge nor pear tree. However, hormone therapy is highly effective in decreasing menopausal hot flashes. Is

there any way to keep cool without the clots and cancer? In the U.S., menopausal hot flashes are considered inevitable, but there isn’t even a word for hot flash in Japanese. This may be due to their greater consumption of soy foods, but you don’t really know until you put it to the test. Harvard’s Center of Excellence in Women’s Health funded a randomized, crossover trial of a half a cup (118 ml) of unsalted soy nuts a day and achieved about a 40 to 45 percent reduction in hot flashes within two weeks compared to the control group. Given

that a plant-based diet may also be effective for managing menopausal symptoms, researchers decided to combine the two: a plant-based diet plus whole soybeans. In fact, two randomized controlled trials found that plant-based nutrition with a daily half cup (86 g) of cooked whole soybeans can reduce the number of serious hot flashes by 84 to 88 percent within twelve weeks. Overall, most randomized to the plant-based bean group ended up free of moderate-to-severe hot flashes compared to about 95 percent still suffering in the control group. Lots of other things can help. Whole fennel seeds, powdered into capsules to

pit them against placebo in a double-blind trial significantly improved menopausal symptoms at a dose of just a teaspoon (2 g) a day. Fenugreek may also help at a dose of one and a half teaspoons (6 g) a day, though not as much as hormones, but without the side effects. Though fenugreek can make your pee smell like maple syrup, sounds like a bonus! The nice thing about studying spices is that entire servings can be stuffed into a pill, to pit them against placebo. A quarter teaspoon (1 g) of black cumin powder a day led to significant

improvements in memory and other tests of cognition within nine weeks compared to placebo. Black sesame seeds— less than a teaspoon (2.52 g) a day of ground black sesame seeds— stuffed into capsules against placebo, drove down systolic blood pressures by eight points within a month. If sustained, that alone could decrease the risk of stroke by about a quarter. What else can we powder? Strawberries! Osteoarthritis patients were randomized to two ounces (50 g) of freeze- dried strawberry powder versus a fake, strawberry-flavored and colored placebo powder, and, compared to placebo, the real strawberries significantly decreased constant pain, intermittent

pain, and total knee pain, and improved disability and overall quality of life. Osteoarthritis is the most frequent cause of physical disability among older adults, yet how do we treat it? Acetaminophen—Tylenol is considered the first-line pain killer, but guess what: it doesn’t work. I mean—it works, just not much better than a sugar pill, but at least it’s not going to make matters worse, like other things we doctors have cooked up, like steroid injections, which actively worsen joint deterioration and offer no greater pain relief than placebos. Or arthroscopic surgery, which may end up tripling our risk of

ending up having to get a total full knee replacement. I mean so, even if the strawberry study is some total fluke, what’s the worst that can happen, tastier smoothies? And less than a quarter of a teaspoon (~1.25 ml) of ground ginger a day can beat out placebo for joint pain. Researchers conclude ginger, "therefore, is recommended as a safe drug for these patients,” but by “drug” they just mean a couple pinches of the ground ginger you can buy at any store. There was even a study on topical ginger— at least, when applied to the scrotum. Paper-thin

slices of ginger applied over the inflamed testicles, and the researchers were, on the ball, healing nearly three times faster than the control group. There have been more than a hundred randomized, controlled trials on ginger, shown to help with nausea and vomiting and everything from COVID to PMS. Heavy periods, painful periods, migraine headaches, multiple sclerosis, and the list goes on. Bottom line: “Mounting evidence suggests ginger can promote healthy aging.” What about garlic? Clinically proven to protect against those who vant to suck your blood. Literally. A hundred marines were randomized to a clove a day or placebo,

and those on garlic had significantly fewer tick bites. Though sadly, garlic does not appear to help against other bloodsuckers. So far, I’ve touched on preserving your bones, bowels, bladder, hair, hormones, and joints, but preserving your mind is the largest chapter in the book, because dementia is one of our most pressing public health problems and the most feared condition of later life. There’s a common misconception that we have no control over whether we develop dementia, but the good news is that although Alzheimer’s may be incurable, at least it is preventable. There is an emerging consensus, that

“what is good for our hearts is also good for our heads,” because clogging of the arteries inside the brain with atherosclerotic plaque is thought to play a role in the development of Alzheimer’s dementia. This is what our cerebral arteries should look like: open, clean, allowing blood to flow throughout our brain. This is what atherosclerosis in our head looks like. Clogged with cholesterol, closing off our arteries— clamping down on blood flow. What kind of brain arteries do you want in your head? Too much cholesterol in our blood is unanimously recognized to be a risk factor for

the development of Alzheimer’s disease. Those with a total cholesterol of 225 mg/dL or more may have nearly 25 times the odds of ending up with amyloid plaques in their brain 10 to 15 years later. Cholesterol explains how the Alzheimer's gene APOE4 ravages the brain. After all, APOE is the primary cholesterol carrier in the brain. LDL cholesterol in those with bad gene variants of APOE averages 40 points higher, but switch people to a diet lower in animal fat and that cholesterol difference can be effectively smoothed out. So, diet can trump genetics. This may explain the so-called

Nigerian paradox, where they have among the highest rates of the Alzheimer's gene but some of the lowest rates of Alzheimer’s disease. How is that possible? Genes load the gun, but lifestyle pulls the trigger. The paradox may be explained by their low cholesterol levels, probably because of their diets low in animal fat. Human beings may have evolved to maintain an LDL cholesterol level of around 25 mg/dL, but the average in the Western world is approximately 120 mg/dL. No wonder heart disease is the leading cause of death in high income countries, and dementia is killer #2. That

helps explain why the so-called Alzheimer’s gene is the single most important gene when it comes to longevity, too. Which is good news, because even if we’ve been dealt some bad genetic cards, we still may be able to reshuffle the deck with diet. So, in terms of dietary guidelines for the prevention of Alzheimer’s, we should center our diets around vegetables, legumes, fruits, and whole grains. In other words, the dietary pillar of lifestyle medicine: whole food, plant-based, nutrition. Or even simpler, plants, plants, and more plants. Any plants in particular? Note that the directors of Loma Linda’s Alzheimer’s

Prevention Program single out berries and greens. Eating strawberries and spinach can mitigate age-related cognitive decline in rats, but what about in people? When the cognition of hundreds of twins was followed over a decade, consuming the berry pigments in less than a quarter cup (23 g) of blueberries a day or about a daily cup (138 g) of strawberries was associated with slowed cognitive aging by about four years, and nearly all of the randomized controlled trials of blueberries and cognitive performance found improvements in at least one brain domain, perhaps, because blueberry consumption can improve blood flow to

certain critical regions of the brain. Now, the one study that flopped mixed the berries with milk, and we know the addition of milk prevents the artery protective effects of tea and prevents the bump in antioxidants that you’d normally get eating dark chocolate and impairs the absorption of the autophagy-activating compounds in coffee. What about mixing berries and cream? The antioxidant activity of blueberries is not just impaired by milk. Check this out. Researchers found that the total antioxidant capacity of our bloodstream (measured in two different ways) shoots up within an hour of eating a cup-and-a-half (200 g)

of blueberries with water and remains elevated five hours later. With milk, maybe one would expect less of a bump? But in fact, they ended up even worse than when they started. After eating a whole bowl of blueberries, they ended up with less antioxidant capacity in their body— because they ate blueberries with milk. One reason greens may be referred to as an anti-Alzheimer’s plant is because dark green leafy vegetables can also improve blood flow in the brain in interventional trials. Randomize older adults to the greens pigments found in about a cup (12 mg) a day’s worth

of cooked kale and see significant improvements in complex attention, cognitive flexibility. And those randomized to even just a half cup of kale’s worth of the cruciferous compound sulforaphane got significant improvements in processing speed and working memory. Here’s the rate of cognitive decline in elderly men and women eating a serving a day of green leafies, compared to those only eating greens about once every ten days. Are you sitting down? “The rates of decline among those who consumed 1 to 2 servings of greens a day was the equivalent to being 11 years younger… .” So, now are

you sitting down to a big salad? Greens come up in chapter after chapter. What’s the recommendation for preventing age-related macular degeneration, our leading cause of blindness? Or even treating it in its earliest stages? Consume a diet high in green leafy vegetables. We’re talkin’ two to three servings a day, so at least greens at every lunch and supper, with bonus points for sneaking them into breakfast in, say, a green smoothie. In fact, blending greens can triple the bioavailability of a key, vision- protecting nutrient. The main reason greens make it into in my Anti-Aging 8 though, is

because of the nitrates in a serving or two of cooked greens can slow our metabolic rate for the same reason, a little shot of beet juice can help free divers hold their breath longer, because it improves the efficiency of our mitochondria, the little power plants in our cells, allowing us to effectively extract more energy from each breath. Another dietary intervention that has a similar effect on slowing metabolism is calorie restriction. The candle that burns half as bright burns twice as long. But instead of starving all the time, you can just eat a big salad. What

else can greens do? In the Harvard Nurses’ Health Study, the consumption of leafy greens appeared to protect against the development of frailty, and when put to the test in a randomized, double-blind, placebo-controlled trial, the equivalent of two thirds of a cup (158 ml) of spinach led to a significant boost in muscle strength, muscle quality, and muscle mass in older men and women. A single cup (240 ml) of cooked greens worth of vegetable nitrates significantly boosted maximal power and velocity in quads so much it was “functionally equivalent, to acutely reversing the effects of several decades of

aging.” A single cup (240 ml) of cooked greens! Of course, when most people think about maintaining muscle mass into old age, they don’t think spinach, they think protein. But if you put together all of the randomized, controlled trials of adding extra protein to the diets of older men and women, you find no evidence that adding protein increases muscle mass or strength. Yeah, but what if you have sarcopenia, excessive age-related muscle loss? Surely then, protein helps, right? No. No significant effect on physical performance or muscle strength. What does work? Exercise. When it comes to age-related muscle

loss, it’s use it or lose it. But maybe exercise plus protein? No. Protein supplementation does not significantly augment the effects of strength training in older adults. In fact, one of my Anti-Aging 8 is protein restriction. Why do longevity experts like Valter Longo recommend people cut down on protein to live longer? Here’s what Luigi Fontana wrote in his book. He’s the director of another leading longevity research center. Excess protein may not mass your muscles, but it will accelerate aging. How do you boost the pro-longevity hormone FGF21? Dietary protein restriction. How do you suppress the age-accelerating enzyme

IGF-1? You do it through dietary protein restriction. How do you suppress the so-called motor of aging, mTOR? Dietary protein restriction. In fact, protein restriction was the only intervention I could find that could slow down all 11 of the aging pathways, which is good news because it’s easier to cut back on protein than it is to cut back on everything and walk around starving all the time. And, it may even be easier than that. Most or all of the life-extending benefits of protein restriction may be due to just restricting particular amino acids like methionine. In that

case, you could even keep your protein intake the same but just swap sources, from animal proteins like meat to plant-based sources like beans. So, in humans, methionine restriction can be achieved using a predominately plant-based diet, which makes methionine restriction feasible as a life-extension strategy. Of course, drug companies look at this same data and think: What pharmaceuticals can we develop to mimic these dietary interventions? Anything else to maintain muscle mass other than greens and machines? How about cocoa beans! Older men and women randomized to a single tablespoon (22 g) of regular cocoa powder a day experienced

a significant improvement in muscle strength, muscle mass, and all four tests of physical performance. And no, the study was not funded by Hershey’s. Unfortunately, the tastiest cocoa doesn’t work as well. The control groups here were given the same amount of highly Dutched cocoa— alkalized cocoa, where some of the bitter compounds removed in the Dutching process are the very flavonoids responsible for the benefits. But natural cocoa is so good it can improve walking performance in those with peripheral artery disease, not only by improving blood flow, but, as muscle biopsies showed, by improving mitochondrial activity. This is

consistent with improved mitochondrial structure as well in biopsies taken from people’s quads. Though this study was actually funded by Hershey’s. What else can cocoa do? Increase the circulation within our skin, boosting it 70 percent within two hours, after less than a tablespoon. Do that every day and within three months, you end up with significantly improved skin thickness, density, and hydration, but no change in wrinkles. However, keep it up for six months, and you do see an improvement in wrinkles, a significant decrease of wrinkle depth, along with an improvement in skin elasticity within 12 weeks— all

by making your life a little more chocolatey, by just adding some natural cocoa powder to your daily diet. I put it in my oatmeal with some canned water-packed tart cherries for a chocolate-covered cherry sensation. What else can we do for our skin? Well, there certainly are other antioxidant, anti-inflammatory, glycotoxin-free foods; so, when patients inquire about a diet that might contribute to younger-looking skin, evidence supports a recommendation to follow a whole food, plant-based diet. But the most important thing to prevent skin aging is avoid the sun. Exposure to sunlight may account for 90 percent of visible

skin aging. That’s why dermatologists agree there’s nothing more important to slow the signs of aging than to protect your skin from the sun. Check out this trucker, who spent years getting more sun on the left side of his face through the driver’s side window. So, the gold standard is considered to be the use of sunscreens in the daytime and “retinoids” at night. They’re talking about a prescription- only form of topical vitamin-A, also known as all-trans-retinoic-acid, or tretinoin (sold as Retin-A), that has been widely proven to improve skin appearance. The only problem is that it may

kill you. “Topical Tretinoin Therapy and All-Cause Mortality”, a randomized controlled trial had to be stopped early, because significantly more people were dying in the retinoic acid group, compared to the placebo-cream group. When applied topically, 1 to 8 percent is absorbed into the bloodstream. Could it be killing people? While the debate continues as to whether the increase in deaths was just some statistical fluke or a real biological effect, tretinoin continues to be banned in Europe for cosmetic purposes. So, what can we use? Topical niacinamide, also known as nicotinamide, is described as one of the best-studied anti-aging

skin cream ingredients (which is not saying much), but it has been shown to reduce yellowing, wrinkling, blotchiness, and dark spots in aging facial skin, for example, significantly reducing crow’s feet wrinkles around the eyes. This was a split-face study in which 64 percent of the niacinamide-side eye wrinkles had moderate or marked improvement, compared to zero percent of the placebo-side eyes. Topical vitamin C also offers similar improvements over placebo in wrinkles, sallowness, and skin tone or firmness. Unfortunately, vitamin C is unstable in creams, turning an unsightly brown when it oxidizes, limiting its shelf life. So instead, what

the skin care industry does, the skin care industry, they use the stable vitamin C esters or derivatives, but there’s no evidence that these compounds have comparable effects, likely because they’re poorly absorbed and only minimally convert to the active form. But the good news is you can make your own. The 10 percent solution used in the study retails for a ridiculous $127 an ounce (30 ml), but you can make a DIY solution more than two thousand times cheaper by simply buying ascorbic acid in bulk and mixing three grams into 30 grams of water, at a cost

of about a nickel per ounce (30 ml). Drip a few drops into the palm of your hand and use your fingertips to apply it over your face, neck, and upper chest daily. (Just don’t get it in your eyes.) And look, you can do the same thing with niacinamide, which can be even more ridiculously priced. But you can buy it in bulk as well, at a 5,000 percent discount. I can go on and on, and the book certainly does, but let me close out by going back to the basics. From the anti-aging journal Rejuvenation Research: “Finally,

a regimen to extend human life expectancy.” Was it some exotic new stem cell treatment or gene therapy? No, it was a reference to this Harvard analysis. More than a hundred thousand men and women were followed for decades, and even just a few basic lifestyle behaviors appeared to translate into 12 to 14 extra years for the average 50-year-old. Even at age 50, you may be able to add an extra dozen years to your lifespan. Even at age 70, there could still be about ten extra years on the table. And if you clean up your life before

50, nearly 18 years may be up-for-grabs, based on simple common-sense behaviors. That’s the kind of life extension extrapolating from some of these lab animal experiments, but after decades of research and hundreds of millions of dollars later, efforts to translate those results into humans have largely been in vain. Yet, here we are with human data suggesting dramatic life extension is available to all of us. Right here, right now. The trillion-dollar pill that anti-aging biotech has been promising us is here, it just effectively has to be administered in the produce aisle and the gym. Turning back the

clock, not with a drug or a DeLorean, but just by eating and living more healthfully. A midlife shift between the ages of 45 and 64 to even the barest of minimums, the barest of minimums. So, what are we talking about? At least 5 servings of fruits and vegetables a day, walking even just 20 minutes a day, maintaining a healthy weight, and not smoking, can result in a substantial reduction in mortality even in the immediate future. We’re talking a 40 percent lower risk of dying in the subsequent four years. The researchers conclude that making the necessary

changes to adhere to a healthy lifestyle is extremely worthwhile, and middle-age is certainly not too late to act. You hold the power. OK. So, I was only able to get to about 100 studies. Just 12,900 to go! For the other 99 percent, you’ll have to wait for the book. But it’s available for preorder now, and all proceeds I receive from the sales of all my books are donated directly to charity. I just want you and your loved ones to enjoy the longest, healthiest life. Thank you so much.