Somewhere in the not too distant future, a woman and a man meet in a restaurant on their first date. After the nervous tension subsides, everything goes well. The man is 33, he says, and is single for most of that time. And although he doesn't talk about it, it becomes obvious that he wants to settle down and start a family. The woman replies that she is 52 years old, she was married, divorced and had children at the age of 20. He is stunned: she looks his age or even younger. This is the dream of Julie Mattison of the National Institute on Aging (NIA) in the United States. She foresees a time when chronological age will tick every year, but biological age can be translated so that the difference in age ceases to matter, as it is now.
Sounds unusual, but our society has already made great strides towards this goal, thanks to advances in medicine and improved healthy lifestyles. For example, in 2014, a medical study in the United States showed that 16% of people aged 50 to 64 suffer from chronic diseases every day. Thirty years ago, this percentage was 23%. In other words, along with an increase in life expectancy, the length of a healthy life increases. Life is added to years, not years to life.
So what do we need to do to further increase the length and quality of our lives? Scientists around the world are pursuing different ideas, but Mattison and her colleagues believe the answer is simple: diet. They believe that the key to a better old age will be reducing the amount of food on our plates - called calorie restriction. This diet doesn't just cut back on fatty foods from time to time; it is about reducing portion sizes gradually and carefully. Since the early 1930s, a 30 percent reduction in daily food intake has been associated with longer, more active lives for worms, flies, rats, mice and monkeys. In other words, in the animal kingdom, reducing calories has proven to be the best way to prolong life. It is possible that people should take note of this.
The idea that what a person eats determines his health is undoubtedly deeply rooted in the past. But, as is often the case in any scientific discipline, the first detailed observations of this connection came from ancient Greece. Hippocrates, one of the first physicians, stated that diseases were natural, not supernatural, and that many diseases were associated with overeating; fat Greeks, as a rule, died earlier than thin ones, this was evident and written on papyrus.
Spreading from this epicenter of science, his ideas have been adopted and adapted over the centuries. At the end of the 15th century, Alvis Cornaro, a feeble aristocrat from a small village near Venice, Italy, decided to test an old wisdom for himself.
If indulgence was harmful, would dietary asceticism be beneficial? To find out, Cornaro, at the age of 40, ate only 350 grams of food a day, which equals roughly 1000 calories. He ate bread, panatela, or broth with eggs. From meat he chose veal, goat, beef, partridges and poultry. I bought fish caught in local rivers.
Abstaining in quantity but not in variety, Cornaro stated that he had achieved "perfect health" by the time of his death 40 years later. It is believed that he died at 84 - which is impressive for the 16th century, when people in the 50-60 years old were considered old. In 1591, his grandson published a three-volume work entitled Conversations on Sober Living, which revisited aging itself and dietary restrictions.
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Cornaro argued that, having received an additional burst of strength in old age, older people who are fully in control of their mental abilities will be able to pass on his teachings further. With his diet, beauty became the lot of the elderly, not the young.
In search of longevity
Cornaro was an interesting person, but his findings should not be taken for fact in any scientific discipline. Even if he was honest and not sick for almost half a century, which is unlikely, these are just the words of one person.
However, since then, fundamental research in white rats in 1935 has shown that a dietary restriction of 30-50% prolongs life span by delaying the onset of age-related diseases. Of course, what works for rats may not work for humans.
Long-term trials that follow people from an early age until death are rare. “I have no idea that human life span research could become a funded research program,” says Mattison. "Even if you take on people aged 40-50, it will take another 40-50 years for research." In addition, ensuring that extraneous factors - exercise, smoking, treatment, state of mind - do not influence research outcomes is nearly impossible for our socially and culturally complex species.
That's why two independent long-term studies were initiated in the late 1980s - one at the NIA and the other at the University of Wisconsin - to study calorie restriction and aging in rhesus monkeys. Not only do we share 93% of our DNA with these primates, we age the same way.
Gradually, after middle age (about 15 years in rhesus monkeys), the back begins to ache, the skin and muscles begin to sag, and where they still grow, they turn not blackish brown, but gray. The similarities go deeper. In these primates, the manifestation of cancer, diabetes and cardiovascular disease is gaining momentum with age. “These are great models for studying aging,” says Rosalyn Anderson, a gerontologist at the University of Wisconsin.
And they are easy to control. They were fed specially made cookies, so the diets of 76 monkeys at the University of Wisconsin and 121 at the NIA were tailored to their age, weight, and natural appetite. All monkeys received the full range of nutrients and minerals they needed. Just half of the monkeys ate 30% less.
And they could not be called malnourished or hungry. Take Sherman, the 43rd monkey from the NIA. Mattison says that when he was put on a calorie-restricted diet in 1987 at the age of 16, Sherman showed no clear signs of hunger, which his species does well.
The Sherman is the oldest known rhesus monkey, almost 20 years older than the average captive-bred rhesus monkey. As the young monkeys became ill and died, he seemed to be impervious to old age. Even at 30, when he was considered old, he looked and acted differently.
The same is true, to varying degrees, for the rest of his experimental group at the NIA. “We have a lower incidence of diabetes and a lower incidence of cancer in the CR groups,” says Mattison. In 2009, the University of Wisconsin published similarly impressive results.
Their restricted diet monkeys not only looked younger - had more hair, less graying, more brown, less gray - their standard-eating counterparts, they were healthier and inwardly sicker. The incidence of intestinal adenocarcinoma has halved. So does the risk of cardiovascular disease. And while 11 monkeys in the full-fed group got diabetes and 5 got a pre-diabetic condition, blood glucose regulation looked healthier among all the monkeys on a restricted diet. They were not afraid of diabetes.
In total, only 13% of the monkeys in the restricted diet group died from age-related diseases at age 20. In the ad libitum group of monkeys (who received a complete diet), 37% had died by this age, almost three times that number. In 2014, an update of the study showed that the percentage remained the same.
“We have demonstrated that aging in primates can be manipulated,” says Anderson. “This is partly silent because it's obvious, but conceptually it's very important; this means that aging itself is a reasonable target for clinical intervention and treatment.”
If aging could be delayed, all related diseases would follow suit. “Treating one disease or another at a time will not really extend a person's life expectancy, because he will die from something else,” says Anderson. “If you have cured all types of cancer, you cannot save a person from cardiovascular disease, dementia, or diabetes-related disorders. But if you postpone old age, you decide everything at once."
Reducing food intake has definitely affected the health of the monkeys, but limiting calories to humans in the real world is much more difficult. First, our access to cheap, high-calorie food has become much easier. Food can be ordered at home. Weight gains by itself, you don't even need to do anything.
"Genetics is involved in this whole thing and some people find it harder to stay in shape than others," Anderson says. “We all know people who can eat a whole cake and nothing happens. Others are forced to take their pants one size larger.”
Ideally, the amount and type of food we eat should be adapted to who we are - our genetic predisposition to weight gain, how we metabolize sugar, how we store fat, and how we feel about food psychologically. At present, all of this is outside the scope of scientific instructions, and perhaps it will always be so.
But predisposition to obesity can be used as a guide to life decisions, not as an inevitability. “Personally, I have a genetic history of obesity running through my family, and I practice a flexible form of calorie restriction,” says Susan Roberts, a nutritionist at Tufts University in Boston. Nowadays, there are many useful tools that allow you to control your own body mass index and practice calorie restriction yourself.
Not only has Roberts dealt with obesity herself, she knows the benefits of calorie restriction better than anyone else. She has been Lead Scientist at Calerie for over 10 years. 218 healthy men and women aged 21 to 50 were divided into two groups for two years. In one group, people were allowed to eat whatever they wanted (ad libitum), in the other - 25% less. Medical checks were carried out every six months.
Unlike the rhesus monkey trials, two years of human trials fail to determine whether calorie restriction reduces the onset of age-related diseases. There is simply not enough time for their development. But Calerie's trials have been tested for the first biological signs of heart disease, cancer and diabetes.
Published in 2015, the results after two years of testing were very positive. In the blood of people with limited calories, the ratio of "good" cholesterol to "bad" cholesterol rose, TNF molecules decreased by 25%, and insulin resistance, a sure sign of diabetes, dropped by almost 40% compared to people who ate normally. Overall, blood pressure also dropped.
Admittedly, some of the benefits can come from weight loss. Calerie's earlier studies included obese people as well as people with a body mass index (BMI) of 25 or below, and losing weight definitely had a positive effect on heavier participants. It became obvious that being overweight or obese is bad. Diseases and disorders that used to be associated with diseases of the elderly are now associated with obesity.
Recent results have shown that significant health benefits can also be obtained in an already healthy human body that is not underweight or overweight. That is, a person with a BMI between 18.5 and 25.
Despite these results, more research evidence is needed before advising people to refrain from consuming extra calories. And, obviously, any diet should be approved with a doctor.
In the meantime, scientists will hope that their rhesus monkeys can help us understand why caloric restriction is such a thing. With nearly 30 years of life and mortality data and blood and tissue samples from nearly 200 monkeys, scientists have a lot of work at the NIA and the University of Wisconsin to look into the black box of calorie restriction and highlight how it slows aging.
Should the metabolism be more efficient with what it has if the body gets less food? Is there a common molecular switch that regulates aging that turns on (or off) when the calorie intake is lowered? Or is there an as yet unknown mechanism underlying our life and death? The importance of Sherman monkeys outweighs the importance of their lives.
Answers to such questions will not appear immediately. “If I cloned myself 10 times and we all worked around the clock, I don't think we would find the answers,” Anderson says. "Biology is extraordinarily complex." It is worthwhile to try to understand how calorie restriction and other therapies work. Aging can be treated directly without the need for calorie restriction, and it truly is the holy grail of biology.
Despite the lack of a clear explanation, calorie restriction is one of the most promising ways to improve health and life expectancy. “There was nothing that made us decide that calorie restriction didn't work for people,” says Roberts. Unlike drugs, it also has no side effects. “Our people weren't starving, their mood was great, their sexual function was also. We looked for flaws, but we didn't find them,”says Roberts.
One of the anticipated problems was a slight decrease in bone density, which is often associated with gradual weight loss, says Roberts. But as a precaution, the volunteers received small calcium supplements throughout the process.
ILYA KHEL