Caruso’s Fountain Back to Molochio Drive an hour and a half north from the southernmost tip of Italy and you’ll reach a little town called Molochio in the region of Calabria. Its name is probably derived from the Greek word molokhÄ“, meaning “mallow,” which is a medicinal plant with a bright purple flower. In the central piazza, there’s a fountain you can safely drink from, its cold water flowing via underground springs directly from the Aspromonte mountains. 

In 1972, when I was five years old, I spent six months in Molochio with my mother , who had gone there to stay with my ailing grandfather. For many years , my nonno Alfonso had neglected a hernia, a simple condition that could have been treated with the right care. The day he died, everyone was calling his name to wake him . 
I walked in the room and said, “Can’t you see that he has died already?” 

I was very close to my grandfather, and his death caused me great sadness; but even as a child, I felt that dealing with aging and death was something that I was supposed to do, that I had to take charge of the situation somehow. 

Our neighbor in Molochio, Salvatore Caruso, was about the same age as my grandfather. In 2012, forty years after my grandfather’s death, Salvatore and I would appear in the same issue of the scientific journal Cell Metabolism for my group’s discovery that a low-protein diet, based on the eating habits of Molochio’s elders, is associated with low cancer and overall mortality rates in the US population. 

The cover image of 108-year-old Salvatore standing among the Calabrian olive trees made the pages of The Washington Post and media around the globe. Two years after that, Salvatore was the oldest man in Italy, and one of four centenarians living in Molochio. Since there were only around two thousand people living there at the time, this meant Molochio had one of the highest proportions of centenarians in the world (four times that of Okinawa, Japan, which is believed to have the highest rate of centenarians for a large region). 

Salvatore, who died in 2015 at the age of 110, started drinking from Molochio’s fountain soon after he was born in 1905; given the exceptional longevity of so many of the town elders, it’s tempting to think it might be the closest thing we have to a real fountain of youth. But while that’s an interesting thought, I’ve spent most of my life studying the science of living long , and the truth is nothing so enchanted. You don’t need to travel to Molochio to drink from its fountain of youth— but if you did, you would learn many of the secrets of longevity from its centenarians. 

1.1. The fountain in the piazza of Molochio From Tradition to Science Whether 
by luck or destiny, my life took a path that has given me a unique and invaluable perspective on different diets and cultures. 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. Although I didn’t know it at the time, I grew up between two places that boast among the healthiest traditional diets in the world. Unlike other regions of Italy famous for their meats (Tuscany) or their heavy cream-based sauces (Lazio, Emilia-Romagna), Liguria and Calabria maintained a cuisine based on complex carbohydrates and vegetables, with dishes like minestrone, pansotti al sugo di noce (a ravioli-like pasta with vegetable filling served in a walnut sauce), and farinata (garbanzo beans and olive oil). 

During the summers of my childhood in Calabria, we lived simply ; 
almost every morning my brother or sister or I walked up the hill to the bakery to buy fresh bread, hot from the oven , dark from the whole wheat from which it was made. About once every other day, for either lunch or dinner, we ate pasta e vaianeia, which consisted of a small amount of pasta tossed together with large amounts of vegetables, particularly green beans cooked in the pod. Another common dish was stoccafisso, or stockfish— a dried cod similar to baccala but without the 
salt— served with a vegetable side dish. Other common ingredients of our diet growing up were black olives, olive oil, and lots of tomatoes, cucumbers , and green peppers. Meat was a once-a-week treat; only on Sundays would we have homemade maccheroni pasta with polpette (meatballs)— two each— or sometimes a small steak. 

The most common drinks were water (from the mountain spring), local wine, tea, coffee, and almond milk. We often drank goat’s milk instead of cow’s milk in the morning. Between meals we were allowed to snack only on peanuts, almonds, hazelnuts, walnuts, raisins, grapes, or corn on the cob. Once we finished dinner around 8 p.m., we usually wouldn’t eat anything until the next morning. Even at our celebratory village fairs, the sweets were made with nuts and dried fruit. 

And instead of ice cream, we would often have granita, the frozen dessert somewhere between a smoothie and a sorbet. Made with lots of fruit, it is, in my opinion, the best dessert in the world, but it does contain a lot of sugar. We had to go six miles down the road, to the town of Taurianova, to find the good one. 

The traditional diet of Genoa and its region Liguria is arguably as healthy as that of Calabria’s; low in sugar, it consists of a lot of vegetables, garbanzo beans, olive oil, anchovies, codfish, and mussels, all of which represent important components of the Longevity Diet I present in this book. 

From Ligurian to Chicagoan When I was twelve years old, I would lock myself in my room with my electric guitar, turn the amplifier up to ten, and play along to the albums of Dire Straits, Jimi Hendrix, and Pink Floyd. I dreamed of going to America to become a rock star. That opportunity came in 1984 when, at age sixteen, I left Genoa to live with my aunt in Chicago. 

A music-crazed teenager, I arrived in the Little Italy district of Melrose Park, in the Chicago suburbs, with my guitar sticking out of my backpack, lugging a portable amp. My spoken-language skills were so bad that the immigration official stamped “no English ” on my passport. Chicago had an incredible music scene. I took guitar lessons with Stewart Pearce, an iconic local bebop player. 

I was mostly interested in rock, but I knew that learning to play jazz and bebop 
would make me a much better rock guitar player. On weekends, I would sneak out of my aunt’s house and take the L train downtown, where I would plug in and jam with musicians in blues clubs all night long. 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.” At the time, I knew nothing about nutrition and aging, but I remember thinking something must be wrong with the Windy City diet because so many of my relatives there— mostly ethnic Calabrians—were dying of cardiovascular diseases, which were relatively uncommon in southern Italy in general, and were particularly rare in my extended family. 

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. 
Although I never became obese, I ate like everyone else and grew a lot during my three years in Chicago. My height shot up to six feet two, almost eight inches taller than my father and four inches taller than my brother. A possible explanation for this was all the meat suddenly in my diet , which, along with protein, probably contained steroid hormones. 

I graduated high school in Chicago and headed south to study jazz performance at the famous University of North Texas College of Music. I could never have imagined eating more or becoming bigger than I was in Chicago— until I joined the Army Reserve as a way to pay for my education in Texas. Arriving for boot camp in Fort Knox, Kentucky , 
I joined a battalion of Army tankers who trained with the Marines and took pride in pushing themselves to the limit. We slept only three or four hours a night, did push-ups and other vigorous exercises all day long, and we ate— a lot. 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.

The Army diet was based on meat and carbohydrates, with sugary sodas allowed as a reward only if we had a combined run, push-up, and sit-up score of 200— which meant about seventy push-ups and sixty sit-ups in under two minutes each, plus running two miles in under ten and a half minutes. In retrospect, I can see how addicted we all were to sugary drinks; we craved that mix of phosphoric acid, caramel coloring, and sugar, and everyone envied the very few who could reach that 200-point mark. 

This diet, along with the grueling exercise regimen, made me a lot bigger, increasing the size of my muscles and making me stronger— at least that’s what I assumed at the time. As I will explain in more detail in a later chapter, 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. In the ten years after basic training, during which my diet consisted of a lot of meat, fats, and proteins, my strength and stamina were dramatically reduced. 

But then I slowly switched to the Longevity Diet, and more than twenty-five years later I can do about the same number of push-ups and sit-ups as I did at boot camp when I was nineteen and supposedly in peak shape. My stint in the Army eventually got me interested in how and why different types of diets can improve health without negatively affecting muscle mass and strength. The answer lies in nutritechnology, a new field I have helped create, in which we treat ingredients found in normal food as a complex set of molecules that, in specific doses and combinations , can have drug-like beneficial properties that we can harness to delay aging and prevent disease. 

1 In Tune with Evolution My destination after finishing boot camp was Denton, Texas, just north of Dallas, home of the University of North Texas and one of the largest and best jazz performance programs in the world, where I was set to pursue an undergraduate degree in jazz performance. The program was tough, requiring an all-out, sixteen-hour-a-day, seven-days-a-week effort as a freshman. Jazz greats like pianist Dan Haerle and guitarist Jack Petersen became my teachers. 

Many people in my career as a scientist who know about my beginnings as a jazz musician wonder how I came to make such a drastic change in my life’s direction. 
The truth is, though music and science are obviously very different, you might be surprised at how much my musical training has helped me in the lab and spurred me on to discoveries that required creative approaches. 

If you’re trained from childhood to recognize chords, the ability to recognize frequencies and intervals isn’t that difficult. It’s like learning a new language, akin to a child recognizing spoken words and understanding what is being said. However, I was a mostly self-taught guitar player who learned through listening, so being all of a sudden exposed to a new language was particularly challenging for me; in the jazz program, 
I learned how to understand and write in a language I had always known simply as sound. Similarly, as a scientist , you are always observing; but that observation is useless if you can’t transform it into data or hypotheses. Musical training turned out to be essential for many of the discoveries I made about why we age and how it’s connected to nutrition. 

When I started my research on aging, everyone could see that organisms aged, and everyone suspected that genes were somehow involved in that process; but the scientific community had no idea how to translate these observations into quantifiable genetic and molecular explanations. What were the harmonies and melodies of life and death? 

How could we decipher and transcribe these incredibly complex processes so that we might act upon and change them? 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. 

Another advantage musical studies gave me as a scientist was a training in improvisation and composition, important elements in jazz, to be sure, and also in science; improvisation challenges you to understand what you hear in relation to what you play so thoroughly and instantaneously that you can react to and match it on the fly. But this is only the start, since in jazz eventually the improvisation breaks free from the chord progression, often violating rules that would never be violated in classical music. However, the improviser is always aware of the chords, and the violation must follow new rules, albeit much more flexible ones. 

In science, this skill keeps you on the lookout for ideas that might be new or surprising but that are also well grounded, as opposed to looking for trendy discoveries that are just variations on previous breakthroughs. Composition instead forces you to write music that no one has written before; but unlike with improvisation, the music must be structured, and all the melodies and harmonies, as well as the instruments playing them and the way they are played, must be defined. In science and medicine, the music composer approach pushes you to look for new ideas, new hypotheses, but it also requires that the intervention has a mathematical foundation and is in harmony with the human body and its history. 

I call this being in tune with evolution. For example, as I will discuss elsewhere in the book, 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 
rediscover to promote coordinated changes that do not disrupt the harmony of the human body. Without scientists and researchers thinking outside the box and being open to new possibilities and ideas, many of the greatest scientific and medical discoveries could never have been made—from Alexander Fleming’s discovery of penicillin, to James Watson and Francis Crick and others’unraveling of the structure 
of DNA.

It was at the University of North Texas that I decided to switch my studies from music to science. One day during my second year there, an academic counselor asked me when I was going to enroll in Music Teaching, a course in which I would have to direct a marching band. It was the marching band that decided it. 

I had no intention of ever leading a marching band! For one thing, I was a rock musician. But for another, was this really what I wanted to do with my life? 
All of a sudden I didn’t think so. I still play guitar to this day, but after a few days of wandering the streets of Denton, Texas, I decided that I wanted to devote my life to the study of how we age—or rather, how we might stay young and healthy for as long as possible. 

I had noticed people I knew in their thirties worrying about “getting old.”And it seemed like forty was the age at which people started to become vulnerable to major disease. As a twenty-year-old, I wondered: Why can’t we push that back to fifty, sixty, even further? The field of aging provided a fantastic opportunity. It combined the impossible scientific task of understanding why we grow old and die with the idea I was just beginning to understand: that if we can effectively act on the aging process, we can postpone and even prevent many common diseases, enabling people to stay young and healthy as long as possible. 

Along with my musical training, another element of my background has helped me in my career, and that is self-doubt. After making the decision to switch programs, I went to see the chairman of the biochemistry department, excited to discuss my new program of study. He was, to put it mildly, highly skeptical of a jazz performance major who had never taken a biology course, who now wanted to transfer into the biochemistry program to study aging. 

He told me that I was crazy and that I wouldn’t last a semester. His reaction gave me pause—maybe he was right. My father was a policeman, and my mother, as was the cultural norm when I grew up, ran the house and only worked occasionally as a tailor; neither of my parents, who had emigrated to Genoa from the south, had more than a primary school education. 

So I wasn’t sure I could do it. Maybe I was being presumptuous; 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.”On the one hand, I teach my students never to trust their results, nor those of others, and always to expect that something will go wrong—the great result they might be so excited about will probably change under further scrutiny and experimentation, or when looked at from a different angle. 
On the other hand, 
I teach them that everything is possible. Think of big ideas; if you can dream it, you might be able to do it.

Our popular culture depicts scientists as confident-leader types, sure of what they’re doing and the outcomes they will achieve. And it’s true that this is a mind-set I frequently encounter at universities and in hospitals. Even in my college days, though, I understood that confidence was a way for arrogance to usurp knowledge. 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. 

I didn’t let my doubts stop me back then, and a year later I was thriving in the biochemistry program, working in the lab of the same doctor who had so doubted me. Soon I would be driving sixty miles a day to work in the lab of Dr. Robert Gracy, a leading aging research expert in Texas, where I would begin studying one of the most important aspects of aging: the process by which proteins are damaged. 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.

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