The scientific explanation for longevity

“The Longevity Diet: Slow Aging, Fight Disease, Optimize Weight” by Valter Longo, PhD

Two weeks ago I received a phone call bearing a bad news, that my dear aunt just got diagnosed with cancer. And immediately I search for more information on this disease, in the hope that perhaps besides the standard medical treatment from the hospital I can find something else to complement the doctor’s treatment.

During my research, I stumbled upon the idea of 72-hours fasting, which claimed to be able to reset our immune system and fight diseases, even tumor and cancer. And one of the papers that caught my eyes happens to be written by none other than Dr. Valter Longo, the director of the University of Southern California Longevity Institute in Los Angeles, and the Program director on Longevity and Cancer at IFOM (Molecular Oncology FIRC Institute) in Milan, who has more than 30 years of expertise in the field of longevity.

And I thought, hang on, I know this name from somewhere. And true to my Tsundoku nature, a quick glance on my Kindle library shows me that I already purchased this book few years ago during my early hype of healthy living. Funny how few years ago I was trying to read this book but find it hard to start, and so I stopped. But this time around, this is exactly the book that I was looking for and it’s so easy to read. You know what they say, books can appear at the right time and at the right circumstance, just when you need them the most. So, this is it, this is the book to read!

As Dr. Longo remarks, “one of the primary ways to achieve [staying fully functional into our nineties, hundreds, and beyond] is to exploit our body’s innate ability to regenerate itself at the cellular and organ levels.” And he argues that no matter how badly we eat in the past, these built-in mechanisms can be turned back on quite easily using Fasting Mimicking Diet (FMD) within his Longevity Diet formula (more on this later). This is what this book is essentially about.

Dr. Longo dedicates several early chapters to explain his methodology, the progress of his studies, including the personal story on how he switch from one lab to another. In these chapters he also provide his semi-autobiography that explains where his thinking and scientific approach is coming from. Born in Genoa, Italy, he often spend childhood summers in his grandfather’s place in a nearby Italian village of Molochio where he experienced 2 different types of healthy diets. He then moved to Chicago and later Texas for his university days where he adapted to an unhealthy eating habit.

I like the fact that he was very honest about his journey, especially when switching from a music major to science at university, where his imposter syndrome in this new field turned him into a very diligent “paranoid” person who has to check and double check every experiments that he did and the findings that he discovered.

This careful approach towards science is reflected in his methodology on conducting his research, in what he called 5 pillars of Longevity, where he has to screen any hypothesis through 5 layers of filters: 1. Juventology (basic research) 2. Epidemiology (the study of the causes and important risk factors for diseases in defined populations) 3. Clinical studies (testing the hypothesis in a randomized, controlled clinical trials) 4. Centenarian studies (cross check the data with the habits of those who live until 100+ years) 5. The study of complex systems from outside medicine, as a point of reference and useful analogies.

And so, what are his findings that came out from decades of experience and multiple testing that survived the 5 filters? Here are some of the most important ones, quoted verbatim:

On aging body: 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.
On his experiments on yeast: 1. If I starved yeast—by removing all the nutrients available to them and giving them only water—they lived twice as long 2. 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.
Aging is the cause of most critical illness: 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.
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 [what causes disease at the molecular and cellular level] is like trying to fix a car without knowing how its engine or electrical system works.
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.
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: 1. The longer-lived plane would need more fuel and more maintenance for each mile it flies to prevent damage 2. 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: 1. People who live longer would need more energy to perform more maintenance (DNA repair, cellular regeneration, etc.) 2. People who live longer would need to get better at utilizing energy to increase protection against aging and maintaining normal function for longer.
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?
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.
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 activating aging-related genes, creating insulin resistance, and triggering hyperglycemia.
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.
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.
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.
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 TOR-S6K and PKA genes known to accelerate aging.
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.
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.
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.
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.
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.
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.
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.
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.
Walk fast one hour per day. Take the stairs instead of escalators and elevators, even if you have to go up many flights. On the weekend, try to walk, even to faraway places, but avoid polluted areas. Do moderate exercise for 2.5 hours a week, some of it in the vigorous range. Do weight training or weight-free exercises to strengthen muscles (combined with 30 grams of protein intake following the weight training).
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).
If you starve a cancer patient before injecting chemotherapy, normal cells will respond by putting up a defensive shield. But the cancer cells will ignore the command to kneel and thus remain vulnerable—providing a way to potentially eradicate cancer cells with minimal damage to normal cells.
Virtually all the fasting mice were alive and moving around normally after high-dose chemotherapy. Mice on a normal diet, however, were sick and moving very little after chemotherapy. In the following weeks, 65 percent of the mice that did not fast died, whereas nearly all the fasted mice survived.
What I proposed, and eventually called “differential stress resistance,” was based on the idea that if you starve an organism, it will go into a highly protected, nongrowth mode—this is “the shield.” But a cancer cell will disobey this order and continue growing even when it is starved, because the oncogene is stuck in an “always on” mode.
Diet can also affect the immune system by altering the bacteria population in the gut, which in turn regulates many different immune cells. It’s well established that the Western diet can have inflammatory, negative effects on the types of microbiota occupying the human gut.

Indeed, as you may have guessed, in the latter chapters Dr. Longo dived deeper into the specifics of several different diseases, such as diabetes, cardiovascular, Alzheimer’s, auto-immune, and of course my main reason to read this book: on cancer.

But ultimately, all of his work are presented under the umbrella of longevity. As Dr. Longo explains, “[m]y 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.”

And in the last chapter (chapter 12: How to stay young), he neatly summarized the most important findings and conclusion of his research into a formula of Longevity Diet:

Eat a mostly vegan diet with some fish: Strive for a 100 percent plant- and fish-based diet, but limit fish consumption to two or three meals a week and avoid fish with high mercury content. After age sixty-five to seventy, if you start losing muscle mass, strength, and weight, add more fish and fruit and introduce animal-based foods like eggs, cheese, and yogurt made from sheep’s or goat’s milk.
Consume low but sufficient proteins: Consume approximately 0.31 to 0.36 grams of protein per pound of body weight per day. If you weigh 100 pounds, that is about 31 to 36 grams of protein per day, of which 30 grams should be consumed in a single meal to maximize muscle synthesis. If you weigh 200 pounds and have 35 percent body fat, 60 grams of protein per day are instead sufficient, considering that it is the lean body mass that utilizes most of the proteins. Protein intake should be raised slightly after age sixty-five to seventy in individuals who are losing weight and muscle.
Minimize bad fats and sugars, and maximize good fats and complex carbs: The diet should be rich in “good” unsaturated fats, including those from salmon, almonds, and walnuts, but very poor in “bad” saturated, hydrogenated, and trans fats. Likewise, the diet should be rich in complex carbohydrates, such as those provided by whole bread and vegetables, but poor in sugars and limited in pasta, rice, white bread, fruit juices, and fruits containing carbohydrates that are easily converted into simple sugars. Finally, the diet should be low in animal proteins but relatively high in vegetable proteins, in order to minimize the former’s negative effects on diseases and maximize the latter’s nourishing effects.
Be nourished: The body needs protein, essential fatty acids (omega-3 and omega-6), minerals, vitamins, and sufficient sugar to fight the many wars going on inside and outside cells. To be sure you get enough nutrients, every three days take a multivitamin and a mineral pill, plus an omega-3 fish oil soft gel purchased from a reputable manufacturer.
Eat at the table of your ancestors: Consume a variety of foods to take in all the required nutrients, but choose the ones that were common on the table of your parents, grandparents, and great-grandparents, so long as they are included in the Longevity Diet.
Eat twice a day plus a snack: Unless your waist circumference and body weight are in the normal or low range, it is best to eat breakfast plus one other meal a day and one low-calorie, low-sugar, nourishing snack. If your weight or muscle mass is too low, then eat three meals a day plus a snack.
Time-restricted eating: Restrict your eating to eleven to twelve hours or less per day. For example, if you eat breakfast after 8 a.m., finish dinner before 8 p.m. Shorter periods of feeding (ten hours or less) have been shown to be even more effective in promoting health, but they are much more difficult to comply with and may increase the risk of side effects, such as the formation of gallstones.
Periodic prolonged fasting-mimicking diets (FMD): People who are under seventy years of age, not frail or malnourished, and free of certain diseases should undergo five-day periods during which they consume a relatively high-calorie fasting-mimicking diet (see chapter 6). An FMD may also be appropriate for older people, but only if needed and if a medical doctor recommends it.
Follow steps 1 through 8 in such a way that you reach and maintain a waist circumference of less than 35.5 inches for men and less than 29.5 inches for women. This is higher than the ideal 33 inches and 27 inches cited earlier, but it is more realistic and should still be very effective in reducing disease risk while avoiding malnourishment.

Understandably, the abundance of information is a bit overwhelming at times. Some ever appear to contradict each other, if presented without the contexts. And while the appendix of the book provides various different recipes for Longevity Diet in a 2-week meal plan, we still need to adapt our environment and even ancestral DNA into the meal plan. Hence Dr. Longo emphasis the importance of consulting to nutritionist, dietician, or other experts before undergoing some of the more high risk plans (such as fasting before chemotherapy).

But overall, the wealth of knowledge that I get from this book are very valuable. And who knows it might even contribute in saving my aunt, or at the very least it equip us with better questions to ask to the doctors. I’m forever grateful, Dr. Longo.

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