The Longevity Diet: Discover the New Science Behind Stem Cell Activation and Regeneration to Slow Aging, Fight Disease, and Optimize Weight

by Valter Longo

Epidemiology. This is the study of the causes and important risk factors for disease and other health-related conditions in defined populations. Studying population-based risk factors is crucial to testing hypotheses generated by basic research.

Hypotheses formulated in basic and epidemiological studies eventually must be tested in randomized, controlled clinical trials. This is the gold standard to demonstrate efficacy.

To generate data for the fourth pillar, I have studied long-lived populations in Ecuador and southern Italy and consulted the work of my colleagues focusing on other very long-lived populations in high-longevity zones around the world.

Studies of complex systems. This pillar is the result of my fascination with reductionism, physics, and the need to simplify the human body’s complexity by identifying machines that can serve as models to teach us about the function and loss of function of human organs and systems. This last pillar can complement the others by providing reference points and useful analogies.

But sugars are also the most important nutrient for the human body. Sugar is to the body what gasoline is to a car—the central source of energy. So sugar is not the problem. It’s the intake of excessive quantities of sugar, in combination with proteins and certain types of fats, that contributes to disease both directly and indirectly—by a...

When you look at multidisciplinary studies, you realize that the high-protein, high-saturated-fat, and low-carb diet is one of the worst for your health. Populations with record longevity do not eat this way, and theoretical, clinical, and epidemiological studies supporting this kind of diet’s long-term and longevity benefits are very few.

As you can see, even when a diet is touted as having been clinically studied, it doesn’t mean that it has been studied as rigorously as necessary, so it is always wise to hesitate before adopting a new diet, and to look into how many of the Five Pillars it is based on.

The food you eat can determine how you look and function, whether you sleep well at night, whether you will stay thin or gain weight, and whether your body shape is more like a pear or an apple. The type of food you eat determines whether your brain will use glucose or ketone bodies to obtain energy; and if you’re a woman, the type and quantity of food you eat can affect your chances of becoming pregnant.

It’s important to eat food you truly enjoy, but it’s also important to eliminate or minimize the consumption of food that will make your life shorter and sicker, and to increase the consumption of nutrients that will make your life longer and healthier.

Many ingredients aren’t just food; they’re actually molecules causing remarkable changes in the body—changes in their levels and combinations can repro...

Maybe one day we will determine how old someone is based not on the year he or she was born, but on his or her biological age, which we are starting to be able to accurately measure.

High protein intake, as I explained, causes the activation of the growth hormone receptor, which in turn increases the levels of insulin and insulin-like growth factor 1 (IGF-1), whose altered concentrations are associated with diabetes and cancer, respectively.

Proteins and certain amino acids derived from them, including leucine, can activate TOR-S6K, a set of genes that accelerate aging. Another gene that appears to play a key role in aging is PKA, which we have shown in both simple organisms and mice to be activated by sugars. Mice with reduced PKA activity live longer and are protected against age-related disease.5

By reducing calorie intake, particularly reducing calories from proteins and sugars, you can decrease the activities of the growth hormone receptor, and thus of the TO...

We have known for nearly one hundred years that when mice are fed about 30 to 40 percent fewer calories, they live longer and develop half the tumors and other diseases when compared to the groups of mice receiving a normal-calorie diet.

So, on the one hand we know that chronic caloric restriction can have profoundly beneficial effects on risk factors for many diseases. On the other hand, we know that chronic and extreme diets—diets that reduce calories by 20 percent or more and are maintained for long periods or permanently—can negatively affect necessary processes, including wound healing, immune response, and cold-temperature tolerance. Put simply, besides making a person extremely thin, the detrimental effects of chronic calorie restriction appear to minimize its benefits by causing a major increase in other types of diseases and conditions that are less well understood.

Aim for a diet that is close to 100 percent plant- and fish-based, limiting fish consumption to two or three portions a week and avoiding fish with high mercury content (tuna, swordfish, mackerel, halibut).

Consume 0.31 to 0.36 grams of protein per pound of body weight per day. If you weigh 130 pounds, that comes to about 40 to 47 grams of protein per day, of which 30 grams should be consumed in a single meal to maximize muscle synthesis. If you weigh 200 to 220 pounds and have 35 percent body fat or higher, 60 to 70 grams of protein per day is sufficient, since fat cells require lower levels of protein than muscles. Since this minimum requirement can change from person to person, it is preferable to occasionally consult a dietitian, to make sure that a healthy, lean body mass is maintained.

Finally, the diet should be free of animal proteins (red meat, white meat, cheese) with the exception of proteins from fish, but relatively high in vegetable proteins (legumes, nuts, etc.) to minimize the former’s negative effects on diseases and maximize the latter’s nourishing effects.

in many northern European countries where milk was commonly consumed, intolerance to lactose (the sugar contained in milk) is relatively rare, whereas lactose intolerance is very common in southern European and Asian countries, where milk was not historically part of the traditional diet of adults.

Whether it’s lactose or kale, quinoa or turmeric (curcumin), you have to ask whether these were foods common at the table when you, your parents, or your grandparents were growing up. If not, it’s best to avoid them or consume them only occasionally. The potential problems are intolerances (for example, an inability to break down the lactose sugar in milk) or autoimmunities, such as the reaction to gluten-rich foods like bread and pasta observed in people with celiac disease.

Although clear links have not been proved yet, it is possible that consumption of the wrong foods based on ancestry could be associated with many autoimmune disorders, including Crohn’s disease, colitis, and type 1 diabetes.

Unless your waist circumference and body weight are in the normal or low range, it is best to eat breakfast and one major meal plus a nourishing low-calorie, low-sugar snack daily. If your weight or muscle mass is too low or if it’s dropping against your will, then eat three meals a day plus a snack.

For people trying to lose weight or those who tend to be heavy, the best nutritional advice is to eat breakfast daily; have lunch or dinner, but not both; and substitute for the missed meal one snack containing fewer than 100 calories and no more than 3 to 5 grams of sugar. (Do not skip breakfast, as this has been associated with increased risk for age-related diseases in multiple studies.) Which meal you skip depends on your lifestyle. The advantage to skipping lunch is more free time and more energy. On the other hand, there is the possible disadvantage of restless sleep from having consumed a large dinner, particularly for those who suffer from acid reflux. The disadvantage to skipping dinner is that it eliminates the most social meal of the day.

Another common practice adopted by many centenarian groups is time-restricted eating, or confining all meals and snacks to within eleven to twelve hours or less a day.

You should also not eat within three to four hours of going to sleep.

People under age sixty-five who are neither frail nor malnourished and are free of major diseases should undergo two periods of five days a year in which they consume a relatively high-calorie fasting-mimicking diet, or FMD.

For most people, the Longevity Diet can be adopted simply by replacing a limited number of items with foods that are just as enjoyable, if not more so. Virtually all diets fail because they are too extreme to maintain in the long run. They also fail because they require major changes to your habits and lifestyle.

In a recent study testing many combinations of food components, mice given a low-protein, high-carbohydrate diet lived the longest but also displayed improved health. Mice on a high-protein, low-carbohydrate diet lived the shortest and had the worst health, despite the effect of the diet on weight loss

In our recent study, we showed that simply by lowering protein intake in mice, we can reduce the incidence of melanoma and breast cancer.

Data from studies in mice and simple organisms also support the role of time-restricted feeding and periodic prolonged fasting in lifespan extension and reductions in age-related disease.

Recently we also showed that high sugar levels make heart cells and mice more sensitive to damage and death during chemotherapy, confirming our hypothesis that sugar makes cells more vulnerable to damage.

Most large-population studies show an association between longevity and disease prevention, and a diet that is low in protein; largely plant- and fish-based; and rich in complex carbohydrates, olive oil, and nuts.

consumption of high levels of animal but not plant-based proteins was associated with increased mortality from cardiovascular disease.14 A similar study of forty thousand men suggests that a low-carb, high-animal-protein diet is associated with a twofold increase in diabetes, a finding also consistent with our discovery in the six-thousand-person protein study.

the low-carbohydrate diet caused a much higher loss of water and proteins, indicating that the seemingly large effect of very low-carb diets on weight loss actually represents loss of water and muscle in addition to fat.

I did not have to ask much about his diet, since it was the same as my grandfather’s: dark bread, olives, olive oil, walnuts, almonds, stockfish, tomatoes, and most of all and almost every day, pasta e vaianeia, the pasta dish with lots of vegetables and beans, including green beans in the pod. Variations on this dish still represent the most frequent meals at my own table.

maintaining a high-vegetable, low-protein diet for the first seventy or eighty years of life, and later switching to a diet richer in proteins but also animal-based foods like eggs, chicken, milk, and certain cheeses, may have slowed down aging and optimized the health of the Molochio centenarians.

In either the human body or a car, low fluid level—even of fluids needed for a relatively minor subsystem, such as the radiator—can accelerate aging and cause the whole system to break down. Undernourishment in humans is like low levels of motor oils or other fluids in cars. Another comparison: the car—like the human body—needs both high-quality oils and fuel for its brakes and engine to operate properly. If these products are of low quality or the wrong kind—similar to saturated fats in our diet—the engine and other parts of the car can be damaged and deteriorate faster. Eventually the damage will lead to car problems that must be fixed, just as the aging process in humans leads to diseases.

The Longevity Diet in Summary Eat mostly vegan, plus a little fish, limiting meals with fish to a maximum of two or three times per week. Choose fish, crustaceans, and mollusks with a high omega-3, omega-6, and vitamin B12 content (salmon, anchovies, sardines, cod, sea bream, trout, clams, shrimp; see appendix B). Pay attention to the quality of the fish, choosing those with low levels of mercury. If you are below the age of sixty-five, keep the intake of protein low (0.31 to 0.36 grams per pound of body weight). That comes to 40 to 47 grams of protein per day for a person weighing 130 pounds, and 60 to 70 grams of protein per day for someone weighing 200 to 220 pounds. Those beyond age sixty-five should slightly increase their protein intake, including fish, eggs, white meat, and products derived from goats and sheep, to preserve muscle mass. Consume beans, chickpeas, green peas, and other legumes as your main source of protein. Minimize saturated fats from animal and vegetable sources (meat, cheese) and sugar, and maximize good fats and complex carbs. Eat whole grains and high quantities of vegetables (tomatoes, broccoli, carrots, legumes, etc.) with generous amounts of olive oil (3 tablespoons per day) and nuts (1 ounce per day). See the biweekly diet program in appendix A. Follow a diet with high vitamin and mineral content and complete it with a multivitamin buffer every 3 days. Select ingredients among those discussed in this book that your ancestors would have eaten...

In general, those who reach age one hundred in good health have stayed active or very active into old age. There are of course exceptions. If you look at centenarians, or even just within your own extended family, you will likely find someone who beat the odds: eating whatever they wanted, seldom exercising, yet making it to a ripe old age.

What physical activity is best for healthy longevity? The one you enjoy most, but also the one you can easily incorporate into your daily schedule and the one you can keep doing up to your hundredth birthday and beyond.

Overworking your body is not a good idea. If you consider the “complex systems” pillar described earlier and think about a car, why is it that no one wants to buy a five-year-old car with one hundred thousand miles on the odometer? Because despite being relatively new, it has been driven too much. You can replace the tires and repaint the chassis, but you cannot change every belt, hose, and valve, and there’s a high chance that some overworked component will break down. On the other hand, you don’t want to leave your car parked in the garage most of the time, as this will also eventually cause it to break down. The same holds true for the human body. It’s important to exercise, but not to overexercise, because knees, hips, and joints will eventually get damaged—particularly if you continue to exercise when you feel pain.

Walk fast for an hour every day. The goal of walking for an hour a day can easily be achieved. For example, pick a coffee shop or restaurant fifteen minutes from your work and make a point of going there twice a day. It can also be achieved on the weekend by walking when you would normally drive.

Ride, run, or swim thirty to forty minutes every other day, plus two hours on the weekend. The best way to achieve this goal is to have both a stationary bike and a road bike. When you can, ride outside; when you can’t, use the exercise bike in high gear (use a bike that provides the option of high magnetic resistance, which makes it hard to pedal—as if you were going uphill). After ten minutes, you should be sweating. If you ride on the street, go uphill for at least ten to fifteen minutes. Do this for about forty minutes every other day and for two hours on the weekend.

a long-term study showed that long-distance running among healthy older adults was not associated with osteoarthritis,3 so an injury caused by long-distance running may be less common than we would expect. In fact, another study that followed 74,752 runners for seven years concluded that running reduced both weight and the risk of osteoarthritis.4

Every muscle of the body needs to be used frequently, because muscles grow and maintain or gain strength only in response to being challenged. Climbing six flights of stairs rapidly can cause leg pain, especially if you haven’t done it in a long time. That pain is evidence of minor injury to your muscles. In the presence of sufficient amounts of proteins, muscle injury leads to the activation of “muscle satellite cells” and, eventually, to muscle growth. Muscles can be slightly injured and rebuilt by doing simple everyday tasks that are challenging.

OPTIMIZING ENERGY IN SUMMARY Walk fast for an hour every day. Take the stairs instead of escalators and elevators. On the weekend, walk everywhere, even faraway places (avoid polluted areas as much as you can).

Do moderate exercise for 2½ to 5 hours a week, with some of it in the vigorous range. Most of the beneficial effects appear to be caused by the first 2.5 hours of exercise, making the additional exercise optional. Use weight training or weight-free exercises to strengthen all muscles. To maximize muscle growth, consume at least 30 grams of protein in a single meal one to two hours after a relatively intense weight-training session.

It was a great plan in theory, but when we tested water-only fasting in cancer patients, the three-day trial was not exactly a roaring success. Not because the results were bad—they were in fact very promising—but because the patients, who were undergoing chemotherapy at the time, found it difficult to undergo such an extreme fast, and their doctors and nurses were also very resistant to the idea (see chapter 7 for more on cancer prevention and treatment). So we needed to find a different solution.

In our cancer studies with mice, we had determined that four major changes in the blood need to occur to show that the mouse had entered a protected state as a result of fasting: (1) lower levels of the growth factor IGF-1; (2) lower levels of glucose; (3) higher levels of ketone bodies, the by-product of fat breakdown; and (4) higher levels of a growth factor inhibitor (IGFBP1). To achieve these results (i.e., to mimic fasting), we fine-tuned a diet low in proteins and sugars and rich in healthy fats. We took advantage of many additional nutritechnologies developed in my lab to ensure proper nourishment and maximum therapeutic effects. We called this regimen the fasting-mimicking diet (FMD),