Читать книгу Lifespan - David Sinclair - Страница 9

FOUR
LONGEVITY NOW

EVERY DAY I WAKE UP TO AN INBOX FULL OF MESSAGES FROM PEOPLE FROM ALL over the world. The tide ebbs and flows but always takes the form of a flash flood in the wake of newly announced research from my team or others.

“What should I be taking?” they ask.

“Can you tell me what I need to do to get admitted into one of the human trials?” they implore.

“Can you extend the lifespan of my daughter’s hamster?” I kid you not.

Some of the letters are much sadder than others. One man recently wrote to offer to contribute a donation to my lab in honor of his mother, who had passed away after suffering terribly through many years of age-related illness. “I feel compelled to help, even in some small way, to prevent this from happening to someone else,” he wrote. The next day, a woman whose father had been diagnosed with Alzheimer’s wrote to ask if there were any way to get him admitted into a study. “I would do anything, take him anywhere, spend every last cent I have,” she pleaded. “He is the only family I have and I cannot bear the thought of what is about to happen to him.”

There is great reason for hope on the not-so-distant horizon, but those battling against the ravages of aging right now must do so in a world in which most doctors have never even thought about why we age, let alone how to treat aging.

Some of the medical therapies and life-extending technologies discussed in this book are already here. Others are a few years away. And there are more to discuss that are a decade or so down the road; we’ll get to those as well.

But even without access to this developing technology, no matter who you are, where you live, how old you are, and how much you earn, you can engage your longevity genes, starting right now.

That’s what people have been doing for centuries—without even knowing it—in centenarian-heavy places such as Okinawa, Japan; Nicoya, Costa Rica; and Sardinia, Italy. These are, you might recognize, some of the places the writer Dan Buettner introduced to the world as so-called Blue Zones starting in the mid-2000s. Since that time, the primary focus for those seeking to apply lessons from these and other longevity hot spots has been on what Blue Zone residents eat. Ultimately this resulted in the distillation of “longevity diets” that are based on the commonalities in the foods eaten in places where there are lots of centenarians. And overwhelmingly that advice comes down to eating more vegetables, legumes, and whole grains, while consuming less meat, dairy products, and sugar.

And that’s not a bad place to start—in fact, it’s a great place to start. There is widespread disagreement, even among the best nutritionists in the world, as to what constitutes the “best” diet for H. sapiens. That’s likely because there is no best diet; we’re all different enough that our diets need to be subtly and sometimes substantially different, too. But we’re also all similar enough that there are some very broad commonalities: more veggies and less meat; fresh food versus processed food. We all know this stuff, though applying it can be a challenge.

A big part of the reason so many people aren’t willing to face up to that challenge is because we’ve always thought of aging as an inevitable part of life. It might come a little earlier for some and a little later for others, but we’ve always been told that it’s coming for us all.

That’s what we used to say about pneumonia, influenza, tuberculosis, and gastrointestinal conditions, too. In 1900, those four illnesses accounted for about half of the deaths in the United States and—if you managed to live long enough—you could be virtually assured that one of them would get you eventually.

Today, deaths among people suffering from tuberculosis and gastrointestinal conditions are exceedingly rare. And pneumonia and influenza claim less than 10 percent of the lives taken by those conditions a little more than a century ago—with most of those deaths now among individuals weakened by aging.

What changed? In no small part it was framing. Advances in medicine, innovations in technology, and better information to guide our lifestyle decisions resulted in a world in which we didn’t have to accept the idea that these diseases were “just the way it goes.”

We don’t have to accept aging like that, either.

But even among those who will have the most immediate access to pharmaceuticals and technologies that will be emerging to offer longer and healthier lives in the next few decades, reaching an optimal lifespan and healthspan won’t be as easy as flipping a switch.

There will always be good and bad choices. And that starts with what we put into our bodies.

And what we don’t.

GO, FAST

After twenty-five years of researching aging and having read thousands of scientific papers, if there is one piece of advice I can offer, one surefire way to stay healthy longer, one thing you can do to maximize your lifespan right now, it’s this: eat less often.

This is nothing revolutionary, of course. As far back as Hippocrates, the ancient Greek physician, doctors have been espousing the benefits of limiting what we eat, not just by rejecting the deadly sin of gluttony, as the Christian monk Evagrius Ponticus counseled in the fourth century, but through “intentional asceticism.”

Not malnutrition. Not starvation. These are not pathways to more years, let alone better years. But fasting—allowing our bodies to exist in a state of want, more often than most of us allow in our privileged world of plenty—is unquestionably good for our health and longevity.

Hippocrates knew this. Ponticus knew this. So, too, did Luigi Cornaro, a fifteenth-century Venetian nobleman who could, and probably should, be considered the father of the self-help book.

The son of an innkeeper, Cornaro made a fortune as an entrepreneur and lavishly spent his money on wine and women. By his mid-30s, he was exhausted by food, drink, and sex—the poor guy—and resolved to limit himself in each regard. The historical record is a bit vague on the details of his sex life after that fateful decision,110 but his diet and drinking habits have been well documented: he ate no more than twelve ounces of food and drank two glasses of wine each day.

“I accustomed myself to the habit of never fully satisfying my appetite, either with eating or drinking,” Cornaro wrote in his First Discourse on the Temperate Life, “always leaving the table well able to take more.”111

Cornaro’s discourses on the benefits of la vita sobria might have fallen into obscurity had he not provided such compelling personal proof that his advice had merit: he published his guidance when he was in his 80s, and in exceptional health, no less, and he died in 1566 at nearly (and some sources say more than) 100 years old.

In more recent times, Professor Alexandre Guéniot, the president of the Paris Medical Academy just after the turn of the twentieth century, was famed for living on a restricted diet. It is said that his contemporaries mocked him—for there was no science at that time to back his suspicion that hunger would lead to good health, just his gut hunch—but he outlived them, one and all. He finally succumbed at the age of 102.

The first modern scientific explorations of the lifelong effects of a severely restricted diet began during the last days of World War I. That’s when the longtime biochemical collaborators Lafayette Mendel and Thomas Osborne—the duo who had discovered vitamin A—discovered, along with researcher Edna Ferry, that female rats whose growth was stunted due to lack of food early in life lived much longer than those that ate plenty.112

Picking up on that evidence in 1935, a now-famous Cornell University professor named Clive McCay demonstrated that rats fed a diet containing 20 percent indigestible cellulose—cardboard, essentially—lived significantly longer lives than those that were fed a typical lab diet. Studies conducted over the next eighty years demonstrated again and again that calorie restriction without malnutrition, or CR, leads to longevity for all sorts of life-forms. Hundreds of mouse studies have been done since to test the effects of calories on health and lifespan, mostly on male mice.

Reducing calories works even in yeast. I first noticed this in the late 1990s. Cells fed with lower doses of glucose were living longer, and their DNA was exceptionally compact—significantly delaying the inevitable ERC accumulation, nucleolar explosion, and sterility.

If this happened only in yeast, it would merely be interesting. But because we knew that rodents also lived longer when their food was restricted—and later learned that this was the case for fruit flies, as well113—it was apparent that this genetic program was very old, perhaps nearly as old as life itself.

In animal studies, the key to engaging the sirtuin program appears to be keeping things on the razor’s edge through calorie restriction—just enough food to function in healthy ways and no more. This makes sense. It engages the survival circuit, telling longevity genes to do what they have been doing since primordial times: boost cellular defenses, keep organisms alive during times of adversity, ward off disease and deterioration, minimize epigenetic change, and slow down aging.

But this has, for obvious reasons, proven a challenge to test on humans in a controlled scientific setting. Sadly, it’s not hard to find instances in which humans have had to go without food, but those periods are generally times in which food insecurity results in malnutrition, and it would be a challenge to keep a test group of humans on the razor’s edge for the long periods of time that would be required for comprehensive controlled studies.

As far back as the 1970s, though, there have been observational studies that strongly suggested long-term calorie restriction could help humans live longer and healthier lives, too.

In 1978 on the island of Okinawa, famed for its large number of centenarians, bioenergetics researcher Yasuo Kagawa learned that the total number of calories consumed by schoolchildren was less than two-thirds of what children were getting in mainland Japan. Adult Okinawans were also leaner, taking in about 20 percent fewer calories than their mainland counterparts. Kagawa noted that not only were the lifespans of Okinawans longer, but their healthspans were, too—with significantly less cerebral vascular disease, malignancy, and heart disease.114

In the early 1990s, the Biosphere 2 research experiment provided another piece of evidence. For two years, from 1991 to 1993, eight people lived inside a three-acre, closed ecological dome in southern Arizona, where they were expected to be reliant on the food they were growing inside. Green thumbs they weren’t, though, and the food they farmed turned out to be insufficient to keep the participants on a typical diet. The lack of food wasn’t bad enough to result in malnutrition, but it did mean that the team members were frequently hungry.

One of the prisoners (and by “prisoners” I mean “experimental subjects”) happened to be Roy Walford, a researcher from California whose studies on extending life in mice are still required reading for scientists entering the aging field. I have no reason to suspect that Walford sabotaged the crops, but the coincidence was rather fortuitous for his research; it gave him an opportunity to test his mouse-based findings on human subjects. Because they were thoroughly medically monitored before, during, and after their two-year stint inside the dome, the participants gave Walford and other researchers a unique opportunity to observe the numerous biological effects of calorie restriction. Tellingly, the biochemical changes they saw in their bodies closely mirrored those Walford had seen in his long-lived calorie-restricted mice, such as decreased body mass (15 to 20 percent), blood pressure (25 percent), blood sugar level (21 percent), and cholesterol levels (30 percent), among others.115

110

It seems likely that he had sex at least once again, as he had one daughter, Clara, with his wife, Veronica. L. Cornaro, Sure and Certain Methods of Attaining a Long and Healthful Life: With Means of Correcting a Bad Constitution, &c., https://babel.hathitrust.org/cgi/pt?id=dul1.ark:/13960/t0dv2fm86;view=1up;seq=1.

111

There are other translations. This comes from the edition published in Milwaukee by William F. Butler in 1903.

112

A 3-year-old rat measured in terms of human lifespan would be akin to a 90-yearold human, according to a researcher quoted by the authors. One of their rats, raised on an experimental diet from 6 weeks of age, lived to 40 months, while of those rats raised on a normal diet, the oldest reached 34 months, with “less than a third of the rats in our colony … expected to live to be more than two years old.” T. B. Osborne, L. B. Mendel, and E. L. Ferry, “The Effect of Retardation of Growth upon the Breeding Period and Duration of Life of Rats,” Science 45, no. 1160 (March 23, 1917): 294–95, http://science.sciencemag.org/content/45/1160/294.

113

I. Bjedov, J. M. Toivonen, F. Kerr, et al., “Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster,” Cell Metabolism 11, no. 1 (January 6, 2010): 35–46, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824086/.

114

Among Kagawa’s findings on the impact of Western diets on the Japanese were significant increases in colon and lung cancer and decreases in stomach and uterine cancers, although the subjects’ food consumption was still much smaller than that of Americans or Europeans. When he looked at the residents of Okinawa, they had “the lowest total energy, sugar and salt, and the smallest physique, but had healthy longevity and the highest centenarian rate.” Y. Kagawa, “Impact of Westernization on the Nutrition of Japanese: Changes in Physique, Cancer, Longevity and Centenarians,” Preventive Medicine 7, no. 2 (June 1978): 205–17, https://www.sciencedirect.com/science/article/pii/0091743578902463.

115

Two of the authors of the report were themselves part of the crew who elected to be locked up inside the Biosphere for two years and live on a low-calorie diet, with just 12 percent protein and 11 percent fat in terms of calorie consumption. Despite this calorie restriction and a 17±5 percent weight loss, all eight crew members were healthy and highly active during the two-year period. R. L. Walford, D. Mock, R. Verdery, and T. MacCallum, “Calorie Restriction in Biosphere 2: Alterations in Physiologic, Hematologic, Hormonal, and Biochemical Parameters in Humans Restricted for a 2-Year Period,” Journals of Gerontology, Series A: Biological Sciences and Medical Sciences 57, no. 6 (June 2002): 211–24, https://www.ncbi.nlm.nih.gov/pubmed/12023257.