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

by Valter Longo

One of the primary ways to achieve this is to exploit our body’s innate ability to regenerate itself at the cellular and organ levels.

Unfortunately, the modern diet, and the constant consumption that characterizes the way so much of the first world eats, keeps these built-in mechanisms permanently switched off, leaving us prematurely vulnerable to disease and degeneration beginning in our thirties and forties. But as I’ve discovered over the past thirty years of research, that switch can be turned back on rather easily.

I have now been researching healthy longevity for more than thirty years, studying the links between nutrition and the genes that regulate cellular protection and regeneration. The Longevity Diet collects what I have learned and puts it into a simple program anyone can live by.

I devised a methodology that would ensure the widest possible scientific basis for my recommendations. I call this method the Five Pillars of Longevity. These pillars do not refer to specific interventions such as diet and exercise, but to five disciplines that provide the foundation for my nutrition program: 1) basic/juventology research (juventology, as I will explain, is the science of staying young); 2) epidemiology; 3) clinical studies; 4) studies of centenarians; and 5) the understanding of complex systems (like cars, for example).

with 100 percent of my book royalties going to charity,

Our goal is not to diminish the role of medical doctors in patient care, but to enhance it by providing information on integrative approaches supported by strong animal and clinical data.

Many eager patients have asked whether it’s necessary to buy the products and use them under supervision, or whether they can just do the FMD themselves at home. I always answer the question by first reminding people that half of my program, the everyday Longevity Diet part, consists of foods that can be purchased in any supermarket and does not require supervision or specially formulated products. The Longevity Diet alone will help prevent and treat many diseases, and will also reduce the recommended frequency of the FMD.

The great majority of experts recommend that prolonged fasting periods—anything more than one day—be done only in clinics under the supervision of specialized medical personnel.)

From the Calabrian diet of Molochio, where I spent childhood summers, to the pescetarian Ligurian diet of Genoa, where I was raised, to the heavy American diets of Chicago and Texas, to the health-obsessed diet of that mecca of youthfulness, Los Angeles—I’ve lived the full range of good, bad, and excellent nutrition, which has helped me formulate hypotheses about the connection between food, disease, and longevity.

It also helped me realize that in order to understand how people can live long, healthy lives, we need to go beyond scientific, epidemiological, and clinical studies and investigate actual populations that age successfully.

My exposure to some of the best blues in the world coincided with my exposure to some of the unhealthiest food in the world—what I consider “the heart attack diet.”

These southern Italians in America were eating bacon and sausage with eggs for breakfast, then lots of pasta, bread, and meat for lunch, often having meat again for dinner. They also consumed high quantities of cheese, milk, and high-fat, high-sugar desserts. The famous Chicago pizza had more calories from cheese than from the dough. Drinks were usually sodas or equally high-fructose fruit juices. To make matters worse, much of the food we Chicagoans ate was fried. Not surprisingly, many people I knew were overweight or obese by age thirty.

I spent two summers at Fort Knox doing things I never would have believed myself capable of. It was the toughest and probably the best training of my life. The Army taught me how to get things done quickly, meeting the highest standards while minimizing or eliminating mistakes. Our trainers expected the impossible all the time. If you could do fifty push-ups, they told us, you should be going for a hundred. If you could run two miles in twelve minutes, they’d scream, you should finish in ten. I found out that sometimes when the impossible is expected, it can be achieved—eventually I was able to run two miles in ten minutes.

our recent studies indicate that a protein-rich diet, which can increase muscle size, may not necessarily translate into increased muscle strength and that a periodic low-protein, low-sugar diet, alternating with periods of normal protein intake, may do more to generate new muscle cells (which we currently think has more to do with strength than size does) while promoting health.

As an example of how my music training informed my scientific inquiry, here’s one of my favorite analogies, which I use to explain what’s missing from the prevalent “free radical” theory of aging, which holds that antioxidants alone (higher doses of vitamin C, for example) can extend the healthy human lifespan: Trying to extend your lifespan by increasing your intake of vitamin C is like trying to improve a Mozart symphony by increasing the number of cello players. The cello is a beautiful instrument, but to improve a Mozart symphony, you need to be a better composer than Mozart. Adding cellos alone won’t do it. The healthy human lifespan is much more complex than a Mozart symphony.

It took billions of years of evolution for it to reach the current state of near-perfection. We cannot expect a simple supplement to make something that’s almost perfect even better, so we cannot expect that we will live healthier and longer lives just by drinking orange juice. Not surprisingly, supplementation with antioxidants has not even been shown to extend the lifespan of mice.

if we use a drug that lowers glucose, we are not considering the harmony of the human body, since that drug is disrupting a normal function of the organism. Although this may lead to a temporary solution (lower glucose), in the long run it will usually also lead to problems (adverse side effects). If instead we can rejuvenate the insulin-resistant muscle cells that cause the high glucose levels and render them more functional, we are making changes that maintain and even increase the harmony of the human body.

Further, if this rejuvenation is activated by taking advantage of environments and conditions that echo our past and more ancient organisms, then we are not only taking advantage of the harmony, but we are also “in tune with evolution,” since that process matches the “frequencies” of our history.

Fasting, which is the focus of much of this book, activates coordinated responses that are in tune with evolution because starvation was encountered by all organisms, starting with bacteria, billions of years before Homo sapiens even existed. For this reason, it is clearly one of the most powerful interventions we can redisc...

maybe it was ridiculous to think that I’d be able to keep up. In retrospect, I realize it was probably this doubt that helped me succeed—in the program and as a scientist. My lab’s motto and modus operandi is “paranoia.”

I believe the most revolutionary discoveries come from creativity and doubts because they first appear as crazy ideas, but then undergo a grueling process that makes them real and repeatable.

We can think of proteins as both the bricks that support an organism and the switchboard that transmits biological information from cell to cell, or within cells. For example, growth hormone is the protein that circulates in the blood-activating growth hormone receptors on the surface of cells, which promotes human growth. Like all proteins, growth hormone can be modified and damaged through aging, which can affect its function. Dr. Gracy’s research group was studying how to potentially reverse this protein damage. This study would be the beginning of my research in the extraordinary field of longevity.

The approach in this book is different from that of the great majority of nutrition books because I focus on keeping organisms young, not treating individual diseases or conditions. So it’s important to understand what aging is and the strategies that have the best chance of slowing it down without causing side effects.

“Aging” refers to the changes that occur over time to both organisms and objects. These changes aren’t necessarily negative. In fact, although humans and most other organisms become dysfunctional in old age, growing older can actually bring improvements as well.

Over millions of years of evolution, the lifespan of an organism will tend to get longer if its ability to generate healthy offspring also increases.

Both Wallace and Darwin also hypothesized that aging and death may be programmed so that organisms could age on purpose and die prematurely if it were advantageous to the species—to avoid overcrowding, for example.

We showed that a selfish group of microorganisms—in this case baker’s yeast that had been genetically manipulated to invest in their own protection and live as long as possible—would eventually become extinct, whereas shorter-lived microorganisms willing to sacrifice themselves and die early would seed future generations. In other words, the genetic alterations that make the organism act selfishly and live longer decrease its chances of generating healthy offspring.

we showed that the “altruistic death program” described above is inactivated by starvation, indicating that an organism left without food no longer dies to benefit others, probably because the others are not expected to be around to benefit.

Consider this analogy: Would it be possible to build a plane that could fly years longer than current models without its performance suffering? The answer is yes. There are at least two ways to accomplish this: The longer-lived plane would need more fuel and more maintenance for each mile it flies to prevent damage. The longer-lived plane would require superior technology to reduce damage while using the same amount of fuel and maintenance as current models. Now let’s apply this to humans: People who live longer would need more energy to perform more maintenance (DNA repair, cellular regeneration, etc.). People who live longer would need to get better at utilizing energy to increase protection against aging and maintaining normal function for longer.

we can try to understand how it ages and attempt to slow that down, or we can identify ways to eliminate aged components and periodically replace them with young ones. In this case, it doesn’t matter how the body ages, whether by oxidation or some other mechanism. The goal changes from protecting the body from damage to improving protection and, more importantly, repair and replacement/regeneration.

In both cases the body ages with time, but if we can program health to last longer, the system will trigger protection, repair, and replacement mechanisms to maintain the organism’s vigor and functionality. This is the difference between the current gerontology/aging-based approach and what I think is a more effective juventology-based approach.

To learn how to reprogram longevity though, I had to better understand its molecular mechanisms. The dietary interventions described later in the book are based on discoveries made in part by my laboratory’s research into just this.

We think of yeast as an ingredient in bread and beer, but Saccharomyces cerevisiae (baker’s yeast) is in fact one of the most studied organisms in science. This single-cell organism is inexpensive to work with and easy to study. It is so easy to work with that some scientists carry out yeast experiments at home. It’s also easy to modify genetically, by simply removing or adding one or more of its roughly six thousand genes.

Thanks to the work of Thomas Johnson at the University of Colorado and Cynthia Kenyon at UC San Francisco, it was known that genes could make worms live longer—just not what genes they were or how they worked.

With three Nobel laureates and seven members of the National Academy of Sciences in the pharmacology and biochemistry departments, UCLA was science heaven. I was surrounded by great geneticists, biochemists, and molecular biologists, all ready to help. I didn’t even have to knock, because the doors—even those of the Nobelists—were almost always open.

If I starved yeast—by removing all the nutrients available to them and giving them only water—they lived twice as long. Sugar is one of the nutrients responsible for yeast aging fast and dying early. It activates two genes, RAS and PKA, that are known to accelerate aging, and it inactivates factors and enzymes that protect against oxidation and other types of damage.

Leading science journals refused to publish the findings my mentors and I found so extraordinary, so I used the discoveries as the basis for my doctoral thesis, as well as two other publications, which were ignored for several years. It wasn’t until 1996 that anyone showed any interest in my discovery.

Knowing that “dwarf yeast” with longevity mutations in the growth genes (TOR-S6K) could live up to five times longer than normal yeast, and that “dwarf flies and mice” with similar genetic mutations could live up to twice as long as normal mice, in 2006 I started research on the human version of the growth gene known to correlate to record longevity in mice (see fig. 2.2).

We think of poor nutrition, lack of exercise, and the genes we inherit from our parents as the major risk factors for diseases. But, by monitoring the age at which people are diagnosed with different diseases, we know that aging itself is the main risk factor for cancer, cardiovascular disease, Alzheimer’s, and many other diseases. According to recent data, the probability that a twenty-year-old woman will develop breast cancer within the next ten years of her life is roughly 1 in 2,000. The risk is 1 in 24 for a seventy-year-old woman—that’s an increase by almost a factor of 100.

As I have stated, my approach is different from that of almost all other nutrition books, in that my program doesn’t focus on achieving a healthy weight or on any one specific disease independently of the long-term consequences of a treatment. If aging is the central risk factor for all major diseases, it’s much smarter to intervene on aging itself than to try to prevent and treat diseases one by one.

The lifespan of a mouse is about two and a half years, and tumors begin to appear in mice at the age of one and a half. People live on average more than eighty years, and most tumors begin to appear after age fifty. In relative terms, that is a similar proportion of life. Therefore, we can reduce the risk of cancer and many other diseases by acting on the longevity program, and we now know that we can do this through diet.

To attempt to treat a disease without this information is like trying to fix a car without knowing how its engine or electrical system works.

the most important reason to adopt a diet in the first place: living to a very old age and “dying healthy.” We are so used to associating death with cancer, heart disease, or another illness that the concept of “dying healthy” seems alien. But this is the promise of the “longevity revolution.”

Based on biogerontology (study of the biology of aging), preventive medicine, and longevity research, we now know that the later years of life, even when life is extended, need not be associated with poor health and disease.

I asked her, “Would you fly on an airplane that you had personally designed?” She knew the correct answer to that question was absolutely not. Most planes are designed by teams of world-class engineers working at major aviation companies like Boeing and Airbus, using technology and insights going back to the Wright brothers and even Leonardo da Vinci. Why would you be willing to make key decisions that affect whether you and your loved ones will get cancer, diabetes, cardiovascular disease, and many other illnesses based on the silly idea that one should “eat in moderation”? What does that even mean?

The key to adopting a longevity diet is finding books, like this one, written by scientists or clinicians who have mastered as many of the Pillars of Longevity as possible.

I don’t talk about “miracle diets” or “cures,” and I stay away from fad diets promising weight loss.

I’m confident in these claims because of the positive results achieved by thousands of people I have studied—either personally or through basic research, clinical trials, and genetic and epidemiological studies. I’m also confident because most of my recommendations for everyday diets match the diets of the very-long-lived populations that I, and other experts like Craig Wilcox in Okinawa, have studied. These individuals are concentrated in “blue zones,” a term coined by Michel Poulain and Gianni Pes, and made popular by author Dan Buettner, to identify longevity hot spots, where diet and physical activity levels are believed to be a key factor in successful longevity.

I believe that many popular strategies and diets are inappropriate or only partially correct because they are based on just one or two pillars. This is important because while one nutrient may be protective against one condition or disease, it can negatively affect another, or it can protect middle-age individuals but hurt the very young or the elderly.

Without understanding how nutrients—such as proteins and sugars—affect cellular function, aging, age-dependent damage, and regeneration, it is difficult to determine the type and quantity of nutrients needed to optimize healthy longevity. Without animal studies to determine whether a diet can in fact extend longevity, in addition to having acute effects on general health, it is difficult to translate the basic discoveries to human interventions.