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Want to live till 120?

This professor works on drugs that could get you close.

In what could be a medical revolution, Dr. Nir Barzilai and colleagues are working with the FDA to assess drugs that target aging, not just a particular disease.

- an investigative reporter at The Times of Israel. - December 22, 2015
Nir Barzilai hopes to start his first drug trial in a year (Courtesy)

Experience has in fact borne out that 120 is the upper limit of the human lifespan. Only one person in recent history is verified to have lived longer:
Jeanne Calment of France, who died in 1997 at the age of 122. And who would want to live to 120 anyway if you’re too diseased and decrepit to enjoy yourself? That’s why a variation on the Hebrew blessing says “you should live to 100 as if you were 20,” meaning you should enjoy 100 years of youthful vigor and good health.

Until now, this debate has been academic for most of us, since life expectancy in the developed world is around 80. But Nir Barzilai, MD, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York, believes that in the next few decades it will be possible for many of us to live to somewhere between the age of 110 and 120 by taking drugs that target aging. Not only that, but instead of spending the last five years of our lives shuffling from doctor’s office to hospital, we will live relatively disease-free until the end, then quickly expire of whatever happens to kills us.

“This idea that we can delay aging is a new idea and the understanding that aging is part of every disease is not really well recognized,” he says.

Barzilai is aware that many people think this sounds too good to be true.
It’s not as though turning back the clock isn’t already a multibillion dollar industry and age-old obsession. But bear in mind that scientists have succeeded in slowing down aging in animals like worms and mice. Also, keep in mind that science and medicine have already made great strides in extending our lives. In 1900, the average life span in the United States was 50.

 On November 29, Barzilai and his colleagues starred in an installment of the National Geographic Channel’s “Breakthrough,” a six-part series about cutting-edge work in the fields of robotics, brain science, energy production and medicine. The episode, entitled “The Age of Aging,” was directed by Hollywood veteran Ron Howard. It follows Barzilai and several other researchers of aging as they try to persuade the US Food and Drug administration to allow them to test drugs that don’t target any specific disease but rather what they call “comorbidities of aging.”

According to the FDA, aging is not a disease. Barzilai’s big challenge, therefore, is to get the FDA to approve a trial that targets several diseases at the same time, all of which happen to be associated with aging: diseases like cancer, heart disease, stroke and Alzheimer’s.

“If we can prevent or delay those diseases of aging,” Barzilai tells the Times of Israel, “the FDA will accept it as an end point.”

That’s why he is careful not to use the words “anti-aging,” even if it’s what he really means. The FDA doesn’t like that phrase, not to mention that it’s been associated with what Barzilai calls “charlatans” over the years.

“When I write my grants and talk about my goal, my goal is to prevent diseases. We’re not talking about immortality. We’re talking about why it is in the last 5-10 years of life, people accumulate so many diseases that make their life difficult. They have multiple diseases and multiple treatments and all the treatments are interacting with each other. Why don’t we try to increase the health span? The longevity, if it happens, is only a side effect.”

Why aren’t we living to 120?

In the documentary, Barzilai’s colleague S. Jay Olshansky, a researcher of aging at the University of Chicago, explains that most of our 20th century gains in lifespan were the result of treating infectious diseases like pneumonia, the flu and tuberculosis. The diseases that kill most people nowadays — heart disease, cancer, stroke and Alzheimer’s — require a different approach, which is to tackle the underlying aging process. But money will only start pouring into this approach when the FDA accepts it as a category of treatment.

“Pharmaceutical companies will not come in because medical insurance won’t pay for something that doesn’t have an indication,” Barzilai explains.

Once the FDA agrees that there are drugs that can target the underlying processes of age-related diseases, pharmaceutical companies, biotech companies and venture capitalists will start investing in developing new drugs, he says.

Ashkenazi super-agers

Barzilai was born in Haifa in 1955 and earned his medical degree from the Technion in 1985. After graduation, he was offered a research fellowship at Yale University, where he met his wife Laura. Although they intended to move back to Israel, “life got in the way.” The couple have two grown children, one of whom is a citizen of Israel and the other “a supporter of Israel.”

In the early 1990s, Barzilai was offered a job at Yeshiva University’s Albert Einstein College of Medicine. While there, he discovered a subset of extremely old Ashkenazi Jews living in the neighborhood. He studied over 500 Ashkenazi Jewish “super-agers” between the ages of 95 and 112 to try to figure out their secret.

Barzilai asked the centenarians about their habits and found that they didn’t take any special health precautions.

“Fifty percent of them are obese,” Barzilai explains in the documentary, “fifty percent do not exercise, 60 percent of the men and 30 percent of the women smoke. So it’s in spite of all this that they have some protection that allows them to easily get to age 100.”

In fact, they had several genetic mutations that protected them from chronic fatal diseases. While scientists can’t change anyone’s genes, they can design medications that interfere with the same pathways as those found to be blocked in the centenarians.

How long can we live?

Barzilai says he doesn’t see humans living beyond 120, at least not on the basis of current science.

“As a species we have our maximal life span that is probably somewhere between the ages of 110 and 120, and the question is what do we do with this opportunity?”

The reason, he says, is the second law of thermodynamics.

“Everything on earth disintegrates. Even if we thought of a way to overcome that through regenerative medicine, like stem cells on top of your body, the moment you regenerate the neurons in your brain, those neurons do not store your memories, so basically you become another person. If you’re going to become another person, we already do that by having children, and our DNA is in our children.”

 

When he looks at the centenarians he studied, Barzilai says that they often die like us, of infection, heart disease and stroke, just quicker.

“They’ll be healthy for a long period of time and then just die. There isn’t a long period of pain and suffering. So what we want to do is make the most out of the body we have by delaying aging.”

Drugs to delay aging

There is no shortage of drugs that may be able to do this. The National Institute of Aging has identified at least five compounds shown to slow aging in mice. These include aspirin, acarbose, 17-alpha-estradiol and rapamycin. The drug that Barzilai and his colleagues settled on for their clinical trial is Metformin, widely prescribed to diabetes patients. A UK study last year observed that 78,000 type-2 diabetics in their 60s who took the drug lived longer than a group of healthy people the same age. Even though Metformin is not one of the most impressively performing drugs identified by the National Institute of Aging, it was chosen because it is relatively safe and has few side effects.

Barzilai says the FDA is enthusiastic about the trial and he and his colleagues are working closely with the organization.

In the documentary, he phrases it more Biblically: “I think we are going to the Promised Land — the study will happen. The fact that the FDA will be a major part of it is really an achievement.”

The study is currently in the planning phase. It will start in approximately a year and last 5-6 years.

At present, Barzilai and his colleagues are writing grants to the government to cover the $64 million cost of the study as well as hoping to receive funds from private donors. It will be a double-blind study of about 3,000 elderly people, half of whom will get Metformin and half a placebo. The drug will be assessed on the basis of whether it can delay development of a set of aging-related conditions: cardiovascular disease, cancer, cognitive decline and mortality. If all goes well, in about ten years, the field will be opened for a second generation of more specific and powerful drugs.

 

Barzilai, who is about to turn 60, says “I am very optimistic but I have to hang in there for 10 more years.”

Asked if the second generation of drugs will be so expensive that only the rich will be able to afford to prolong their lifespan, Barzilai predicts that “they will be expensive for the first five years and then become generic, and then there will be new drugs that are even better.”

Soon, predicts Barzilai, we may all become centenarians.

“If you’re healthy at age 100, life is beautiful,” he says, describing the centenarians he studied. “They work, they travel, they do things.”

Prolonging youth?

Yet if most people had their druthers, wouldn’t they want to stop aging at some point in their 20s or 30s, as opposed to being elderly for a protracted period of time?

“The translation of this question,” says Barzilai, “is when do I start Metformin or any other drug that follows it? My study is for ages 65-79 because we want to show that it’s relevant to the elderly and we want to have lots of [medical] events. I cannot start a study at age 30 and see how you are when you get to age 80 because it will take too much time.”

However, there is a study in the UK that is researching the effects of Metformin on people over 40 at high risk for cardiovascular disease.

 

“If the average age in that study is 50 and they have positive results, it will indicate to me that people can benefit from Metformin at a younger age.”

So why shouldn’t everyone just go out and ask their doctor for a prescription for Metformin?“There is no indication that you will benefit from it. The studies still have to be done.”
Barzilai is asked if he lived to 120, how he would use the extra time.

“Let me answer the way one of the centenarians answered when they asked him. ‘As long as my list of plans is greater than my list of achievements, I am still young and still can do things.’”

Barzilai adds that his favorite song is Arik Einstein’s “Ani Ve’ata” (“You and I will change the world.”)

“It doesn’t say,’ I will change the world,’ it talks about collaboration. You need other people to help you change the world. People may have said it before, Arik Einstein sings, but it doesn’t matter. We will start from the beginning.”

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