Can fasting help you live longer? Here’s what the science says.

Mania or cure?

Today’s fasting craze has grown out of more than a century of research showing that extreme caloric restriction – a 20% to 40% reduction – dramatically extends the lives of animals, including worms, flies, mice, rats and rhesus monkeys, from that they get the nutrients they need. No other antiaging intervention comes close. These studies also demonstrate that extremely low-calorie diets significantly reduce the incidence of age-related diseases, especially cancer.

Lab animals are typically only fed once or twice a day – they don’t watch Netflix and they eat popcorn all the time. For decades, scientists ignored the possibility that hours without food could contribute to health and longevity gains among calorie-restricted animals. It is now apparent from what When we eat may be more important to longevity than quantity.

In 2022, scientists at the University of Texas Southwestern Medical Center reported the results of an elaborate four-year experiment tracking hundreds of mice over their lifetimes. Automated feeders allowed some mice to eat as much as they wanted, while sharply reducing the calories of others and allowing the group to have access to food at different times – within a two hour window, within 12 hours, 24 hours a day, day x night. Caloric restriction alone increased the animals’ life expectancy by 10%. Coupled with limiting feeding time to two hours at night, peak activity time for mice, the diet extended their lifespan by 35%. That would translate to about 25 years on average for humans.

It would take decades — and thousands of volunteers with the superhuman discipline to stick to a fasting regimen that long — to determine whether strictly limiting when we eat can buy us that much more time on Earth. But the practice has clear advantages. A 2019 study followed 2,001 heart patients and found that those who fasted routinely were much more likely to be alive four years after a common procedure, cardiac catheterization, compared with patients who never fasted, did so briefly, or stopped many years earlier.

Researchers Rafael de Cabo of the National Institute on Aging and Mark P. Mattson of the Johns Hopkins University School of Medicine reviewed years of clinical trials of intermittent fasting and concluded that there is sufficient evidence of the health benefits that physicians should be trained on the subject and provide guidance to patients.

Of course, what we eat matters too. Researchers at the University of Bergen in Norway recently estimated that a 20-year-old who cuts out hamburgers, hot dogs, white bread and other staples of the Western diet and has a habit of eating beans, lentils, whole grains, nuts, fruits and vegetables can increase your life expectancy by up to 13 years. And like exercise, it’s never too late to start and reap the benefits.

A 60-year-old can gain more than eight years, and an 80-year-old can gain more than three years, scientists say. They did not measure the impact of fasting on life expectancy. But Panda notes that in addition to the physiological changes induced by fasting, discipline encourages better food choices and less snacking.

There doesn’t seem to be a downside to following a 12- to 16-hour interval without eating every night. In 2022, Panda and his colleagues published a study of 137 San Diego firefighters, half of whom agreed to eat only within a 10-hour daily window for 12 weeks. In a region plagued by wildfires, Panda was initially concerned: what if 14 hours without food leaves a firefighter slow or confused during an emergency?

“That was the scariest part for us,” he says. “If any participant feels faint, fails to respond to a 911 call, fails to get into the fire engine within 60 seconds, that would be the end of the study.” But performance has not dropped. Overall, the fasting group showed improvements in cholesterol and mental health and reduced alcohol consumption. Those who had high blood pressure or high glucose at the start of the study saw their levels drop.

“The bottom line is that many of the fasting protocols will have some much better benefit than not fasting at all,” says Panda.

how fasting works

Valter Longo directs the Longevity Institute at the University of Southern California and the Longevity and Cancer Program at the IFOM Institute of Molecular Oncology in Milan. He says his fasting-mimicking diet works in large part by activating blood stem cells, which bolster the body’s ability to produce infection-fighting white blood cells. This does not happen during the foot-and-mouth disease cycle, but when normal eating resumes. The regimen also promotes a cell-cleansing process called autophagy: cells devour their own damaged parts, which are replaced with functional components.

In clinical trials, Longo found that foot and mouth disease switches the body from a sugar-burning mode to a fat-burning mode—essentially rewiring the metabolism, which the modern Western diet has thrown out of whack. Intermittent fasting studies have shown a similar effect, which may explain why people with metabolic risk factors like pre-diabetes seem to benefit more.

About 30 clinical trials around the world are testing FMD in people with cancer, multiple sclerosis, Alzheimer’s, kidney disease, high blood pressure, irritable bowel syndrome, “and almost any disease you can imagine,” says Longo. .

A kit for Longo’s five-day program is also commercially available, for around £162. Longo says all of her profits go to the Milan-based foundation that supports her research. Still, the price puts the package out of reach for many who might benefit — particularly in the United States, where low-income people and people of color have disproportionately high rates of heart disease, cancer and diabetes.

“It’s not scalable,” says Panda. “It’s not going to help the half of the US population that really needs this approach. They cannot pay. They can’t even buy food, healthy food.”

I wondered why Valter Longo decided to bring a new way of eating to a region of Italy famous for centenarians and healthy traditional food. “Currently, few people follow this diet,” says Romina Cervigni, scientific director of the Longo foundation. Around a third of children and teenagers in Calabria are overweight, one of the highest rates in Italy. Sixty-one percent of residents age 65 and older have high blood pressure, 29 percent have heart disease and 24 percent have diabetes, with rates skyrocketing as people reach their late 70s and 80s, according to the system. of chronic disease surveillance established by the Italian Ministry of Health.

“We hope that the study will improve the lives of a new generation”, says Orlando Fazzolari, mayor of Varapodio.

Longo and his team are recruiting volunteers who are overweight and have high blood pressure, high cholesterol, high blood sugar or other metabolic risk factors. The researchers will randomly sort people into three groups. One will eat normally, switching to the fasting-mimicking regimen for five days three times – at the start of the study, three months later and three months thereafter.

The second group will follow the same foot-and-mouth schedule and the rest of the time will eat what he calls a “longevity diet.” It’s nearly vegan, with the exception of some fish, and ideally consumed within a 12-hour daily window. The final group will serve as a control, without changing anything in their diet. The study will measure changes in body mass index, various biological markers and biological aging.

At the end of six months, Longo will invite the control group to switch to the longevity diet. Years of research had taught him that when people volunteer for a study and end up not getting anything that could improve their health, they often feel cheated. The study takes place in villages with a maximum of a few thousand inhabitants and everyone knows each other. He doesn’t want the people in the control group to complain: why did my cousin go on the diet and not me?

Calorie restriction in a pill

No antiaging intervention tested by scientists — and they’ve investigated hundreds — has had stronger, more consistent effects than caloric restriction. It increases the lifespan of rodents by up to 50%. Rhesus monkeys – closer to us than mice, genetically speaking – also benefit. In one study, researchers reduced the daily caloric intake of rhesus macaques by 30% throughout their adult life, without skimping on nutrients. These animals not only lived longer than the monkeys fed standard food, but they were also less likely to develop diabetes, heart disease, cancer and the brain shrinkage that often comes with old age.

In humans, eating the bare minimum needed to survive might prevent or delay some diseases, but in the long run it would cause other problems, such as bone loss. Even if the practice were safe, many of us wouldn’t think that living a longer life would be worth living if it meant walking around hungry all the time. João Pedro de Magalhães, professor of molecular biogerontology at the University of Birmingham, in the United Kingdom, thinks so.

“I suck when I’m hungry,” he says. “I get very moody. So the question is, could we develop a way to get the health and longevity effects benefits of calorie restriction without having to diet? This is something people have dreamed of for decades.”

Now, his lab has taken a step closer to finding an answer. In a series of experiments, de Magalhães and his colleagues showed that a prescribed blood pressure drug, rilmenidine, prolongs the lifespan of the worm. C. elegans by about 20% – and it does so by mimicking the protective biological effects of caloric restriction. The drug activates the same genetic pathways as a super low-calorie diet. It also induces what is known as autophagy, or the shedding of old cells, a process critical to health that deteriorates as we age. The worms lived longer, even if they didn’t take the drug until they were old.

Scientists have studied other compounds that mimic the genetic and molecular action of extreme dieting. Two of the most promising drugs for slowing aging, rapamycin and metformin, act on the same pathways and mechanisms that give calorie restriction its life-extending power. But some experimental compounds that looked promising turned out to be toxic in animals.

De Magalhães uses computational methods to find a possible pill that mimics caloric restriction in the vast repositories of widely used drugs, those that are already proven safe in humans. He found that rilmenidine triggers the same protective molecular effects in mice that he saw in worms, and he plans to study whether it also increases the mice’s lifespan.

He also hopes to investigate the drug’s anti-aging and longevity effects in people taking it for high blood pressure. Does rilmenidine decrease biological age? Does it reduce the risk of other age-related diseases?

Of course, there is a long way from treating worms to treating people. When can we see a pill that safely and effectively tricks the human body into acting as if it were on the merest of diets, even when we eat our fill?

“That’s the million-dollar question,” says Magalhães. “On the one hand, I’m optimistic about it. On the other hand, I am also realistic that the benefits seen in animal models will not fully translate to humans. The effects of lifespan, 20% in worms, will be much more modest in humans. But if we can increase life expectancy just a little bit – and it’s not just about life expectancy – if we can improve the health of the elderly with this preventive measure, that would be a fantastic achievement in itself.”

Can fasting help you live longer? Here’s what the science says.

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