May 12, 2011, Updated September 12, 2012

Israeli study reveals old mice regain a young immune response after being deprived of a certain white blood cell and forced to make more. Now clinical trials are underway.

B-cell rejuvenation

Prof. Doron Melamed thinks B-cells are the key to rejuvenation.

Chinese medicine practitioners have known it for centuries, and new diseases like HIV have educated the world on just how important the body’s immune system is for keeping us fit.

Now researchers in Israel believe they have found that the immune system also may hold secrets to the fountain of youth. They have discovered a way to reverse the aging process using an existing drug that helps rejuvenate B-lymphocytes — a type of white blood cell.

In lab experiments at the Technion-Israel Institute of Technology’s Rappaport Faculty of Medicine in Haifa, Prof. Doron Melamed took aging mice and removed their B-lymphocytes, keeping them in a constant state of B-cell deficiency. As a consequence, the mice were forced to create new B-cells in their bone marrow, and did so as though they were young mice.

The researchers found that these “old” mice showed a 400 percent increased response to vaccines, suggesting something remarkable had happened to improve their immune system. The findings were published in the January 2011 issue of the medical journal Blood.

Clinical studies now recruiting

It’s common knowledge that as the human body ages, its immune system declines, along with a rapid deterioration of B-cells. This deterioration makes us less able to fight off the flu and other immune-related diseases. Perhaps, if scientists could restore B-cell functioning to the level of a 20-year-old, we would live longer and better.

With this belief, Melamed and his associates are eagerly awaiting the results of ongoing clinical trials in 50 or 60 people with B-cell lymphoma at Israel’s Rambam Health Care Campus. So far, things look encouraging.

The study is using Rituximab, sold under the trade names Rituxan and MabThera, which is a drug used for conditions including rheumatoid arthritis. Additional patients for the trial, as well as additional research collaborators, are being sought.

Scientists Arnaud Van Den Broeck and John Cambier from the University of Colorado School of Medicine write that this new Israeli research “may constitute a breakthrough in our understanding of the molecular basis of the age-associated immune dysfunction.”

Consequences of turning back the clock?

Is it possible to slow the aging process? Melamed believes it is. “As with every aging process in the body, it is generally thought that aging of the immune system – including that of the B-cell population – is a progressive process that cannot be stopped and/or reversed,” he says. “But we have succeeded in showing that it is possible to turn back the aging process.”

He tells ISRAEL21c that the approach is not without its potential risks: The immune system has a memory of every pathogen it is exposed to. If we suddenly knock out the B-cell functioning in healthy people to help them live longer, it could have dire consequences should they be exposed to childhood illnesses like chicken pox again, but at an older age.

Fortunately, says Melamed, it’s been shown that this “immune memory” probably is very mildly affected. The unknown is what might happen over a long period of time on the treatment.

“It is too far at the moment to try to think whether or not this kind of treatment could help people with cancer or heart disease. At the moment, we are focusing on whether we are able to enhance older people’s immune response. The major concern is about infectious disease — like the flu, pneumonia, like wound healing. Everything that is related to the immune system is weakened with aging,” he says.

On track to drug discovery

“People suffer a lot with an increased duration of life,” Melamed continues, “so we also want the quality of life to be maintained without visiting physicians, and [without] drugs. At the moment, clinically we can enhance the immune system and one can apply this to cancer. It’s clear that cancer is a failure of the immune system. If by this treatment or something similar, we might be able to find in the future something that is based on our discovery, we could help the immune system fight cancer.”

In the Rambam study, patients are already experiencing B-cell depletion therapy as part of their treatment for B-cell lymphoma, a type of cancer. Ultimately, Melamed would like to bypass the B-cell replacement idea altogether and go deeper into the mechanisms that cause B-cells to age. He plans on targeting the mechanism rather than the B-cells of healthy elders.

“If you are able to identify the mechanism, and if there is a molecule that is involved, we can target the molecule itself to rejuvenate the cells,” he explains.

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Jason Harris

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