The search for the ‘Holy Grail’ of human longevity

By Patty Winsa

Our life expectancy at birth has risen from roughly age 50 to 80 in the past century, a dramatic increase considering that for hundreds of years the human expiration date had been constant, hovering somewhere around 40.

So why do some scientists want us to stop aging?

The reason is they believe aging is the single biggest risk factor for diseases such as cancer, Alzheimer’s and Type 2 diabetes — conditions that were less of a concern before public health improvements such as clean water, vaccines and medication helped us live longer.

If scientists can find a way to slow the aging process, they believe they can delay the onset or progression of a number of those illnesses.

Scientists have already used a drug called rapamycin, as well as manipulated a gene, to extend the life of mice by 10 per cent to 30 per cent. The mice not only lived longer than their typical three years, but they were also in better health, which is really the goal of modern aging research, says Judith Campisi, a cell and molecular biologist at California’s Buck Institute for Research on Aging.

Now researchers in the U.S. and Canada want to hold the first anti-aging clinical trial to see if they can replicate the same effect in humans using a diabetes drug called metformin.

While there is no guarantee that metformin will be successful, the research is part of the quest for the Holy Grail in the fight against aging.

Judith Campisi of the Buck Institute for Research on Aging, says there’s "reason to believe the field is correct in looking for this Holy Grail."

 The proposed metformin trial doesn’t require approval by the U.S. Food and Drug Administration to proceed, but researchers are asking the agency to comment on how it should be conducted because the FDA decides how a drug is labelled and sold.

If the trial goes ahead next year, and if it’s successful, the agency has agreed to label metformin as a treatment for a number of age-related illnesses. It is already sanctioned to treat Type 2 diabetes, after being approved for that purpose in Canada in 1972 and in the U.S. in 1994.

But the label won’t mention anti-aging.

“Neither (the FDA) nor us want to say aging is a disease,” says Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York City. Barzilai, who is the trial’s lead investigator, says instead, “I think of the biology of aging as the risk factor for all of those diseases, and that’s what we want to target.”

The trial could clear up years of uncertainty about the efficacy of metformin as a potential miracle drug.

A decade ago, a study concluded that diabetics taking the drug who then got cancer had a lower than expected risk of death.

In the years since, there have been dozens more studies, but roughly half have failed to reproduce the same findings, says Michael Pollak, an oncologist and professor at McGill University.

In the lab, though, metformin has consistently been shown to slow the rate at which cancer cells divide, says Pollak, who tested the drug in his lab eight years ago. He is the only Canadian involved in the proposed trial.

More recent studies show the drug may suppress chronic tissue inflammation, which is present in almost all of the age-related diseases and which researchers believe could be a common pathway to disease, according to Campisi.

If scientists can find a way to interrupt the pathway, they may be able to stall the disease, says Campisi. “There’s reason to believe the field is correct in looking for this Holy Grail.”

(Scientists in Scotland started a trial this year to see if metformin can prevent Type 1 diabetes.)

If the U.S. trial is successful, metformin or another drug like it could change the way patients are treated, for instance by decreasing inflammation in an elderly person before and after a hip replacement. 

It could also create roles for doctors who specialize in treating several diseases of aging, says Campisi, and replace the “silo approach” to treatment.

“Now people working on aging are thinking we need a brand of physician who is going to look at the much larger picture,” says Campisi. She is featured in The Longevity Book, published this spring and co-authored by actor Cameron Diaz and writer Sandra Bark, which deals with the latest aging research.

A trial could also create strict parameters for future research on anti-aging drugs, which often attract charlatans.

“I have to say outright that a very important take-home message for your readers is that there’s a huge amount of quackery,” says Pollak.

He notes that after research in the 1990s on human growth hormone, the drug began proliferating as an anti-aging formula — one that could purportedly turn back the clock and help build muscle, increase stamina and reduce wrinkles.

Pollak says the hormone does make people produce more insulin-like growth factor 1, which stimulates cell division as well as an increase in cell size.

But “the best research predicts that you will actually age more quickly because all your rates of cell division are higher,” he says.

 

 Dr. Michael Pollak, seen in the department of oncology research lab at Montreal's Jewish General Hospital, is the lone Canadian involved in the proposed metformin trials.  (Giovanni Capriotti) 

 

Magic pills or pixie dust?

Several drugs are being studied as possible boosters of longevity:

Rapamycin (Rapamune)

What it is: The drug is taken by organ recipients to inhibit rejection, allowing patients to take lower doses of cyclosporin, a more toxic immune suppressant.

Research: It was discovered by Suren Sehgal, who worked for Ayerst labs in Montreal, in soil from Easter Island in Polynesia. When Ayerst moved its labs to Princeton, N.J., and Sehgal moved with them, the researcher was supposed to throw away the samples of the bacterium but he kept them in his freezer, next to his ice cream, according to a Bloomberg story. He continued his research at Ayerst in the U.S., and the drug Rapamune was approved.

Aging: Tests are being done on the drug in dogs. Testing on mice showed they lived longer and were healthier — “impressively so,” says Judith Campisi. But they also suffered serious side-effects such as cataracts and, in males, testicular atrophy. “And I bet half the population would be very alarmed by that,” she says.

Metformin

What it is: The drug helps control blood sugar levels in Type 2 diabetics.

Research: Oncologist Michael Pollak set out to study metformin in his McGill lab eight years ago because he didn’t believe U.K. studies that found diabetics on the drug had a lower risk of dying from cancer. “We made cancer cells grow more slowly by using metformin. It’s true,” he says, noting that in controlled studies in petri dishes, “it always works.” But Pollak says only half of the human studies done after the U.K. research found the same results.

Aging: Metformin is fairly safe, says Pollak, who sees it as a good candidate for a clinical trial. “You have to be very careful if you’re recommending long-term use of a brand new compound that’s never been given to anyone. If you’re a healthy 60-year-old, are you going to start taking it?” he asks. “Absolutely not. The only reason metformin is interesting to date is because we have millions of patient-years (of) experience.” There are rare serious side-effects.

Resveratrol

What it is: A chemical found in red wine, the skin of red grapes and dark chocolate.

Research: The drug was shown to extend the life of lab mice after they had been genetically manipulated and fattened up so that they would get clogged arteries. There is no evidence the chemical does anything in people, says Campisi.

Aging: “It got a lot of press, that this was the longevity drug,” says Campisi. “And of course the French loved it because it’s present in red wine — except you’d destroy your liver if you ever drank enough red wine to give you a therapeutic dose.

“But that’s OK,” she says wryly. “We can transplant your liver and give you rapamycin and you’ll be fine.

“There is a lot of hype about drugs like resveratrol,” Campisi notes. “A lot of work needs to be done.”

 

Aging research now a mature field

Research on aging was already happening by 1935, when scientists looking for the fountain of youth experimented on rats to see if calorie restriction improved lifespan. Other major studies include:

• Baltimore Longitudinal Study:America’s longest-running observational study on aging began in 1958. Participants are assessed by doctors every one to four years depending on their age. The study seeks to identify common factors that lead to aging, disease and ways to intervene in the aging process and age-related disease.

• Canadian Longitudinal Study on Aging: The world’s largest longitudinal study is getting off the ground after a three-year period of recruitment. Fifty-one thousand men and women between the ages of 45 and 85 were enrolled. Although the focus is to improve care and help seniors stay in their homes longer, the study will also record the genetic information of participants and could lead to the discovery of common genes in people who live longer.

• Calico: The project was founded by Google in 2013. By many accounts, Google has hired some of the best anti-aging scientists in the U.S., but the organization won’t say what it’s doing at present. When the Star asked for an interview, the Google press team responded by saying in an email, “Calico is heads down and 100 per cent focused internally right now, so isn’t pursuing any media opportunities."