Israeli scientists discover how to reverse cell aging

Prof. Doron Melamed, together with doctoral student Reem Dowery, sought to understand why the elderly population is more susceptible to severe cases of COVID-19 and why the vaccines seem to be less effective and wane faster among this population. 

The results of their work were published this month in the peer-reviewed journal Blood.

The secret begins with B cells, also known as B lymphocytes. These are the cells that produce antibodies against any pathogen that enters the body. They play a key role in protecting people from viruses and other diseases.  

B cells are produced in bone marrow, then travel through the blood to lymph nodes and spleen, where they wait for pathogens to enter and then attack them.

“When you are young, you have young cells and young cells have a very diverse ability to recognize anything that comes into your body,” Melamed explained to The Jerusalem Post.

B cells do not live long. Rather, they are constantly being replenished by new B cells sent from the bone marrow, creating what Melamed calls “homeostasis” – the total number of B cells in the bone marrow and outside remains stagnant. 

However, B cells don’t just disappear. They turn into “memory” B cells so that if the body is exposed to a previous pathogen, the individual will not get sick. That’s because the immune response will be fast and robust and eliminate the pathogen – often without you even feeling you were exposed. 

Unlike B cells, memory cells are long-lived. 

“Imagine you are growing into adulthood, and you become an adult and then an older person,” Melamed said. “You accumulate in your body many memory cells. You are exposed all the time to pathogens and hence you make more and more memory cells. Because these are so long-lived, there is no room left for new B cells.”

So, what happens when a new pathogen, like the coronavirus, comes along?

There are no young B cells that can recognize it.  

That is one of the reasons why older people are more susceptible to severe COVID-19 and many other diseases. 

As noted, this happens because of the body’s need for homeostasis, something that Malamed’s lab discovered a decade ago. 

But this year, it took the discovery another step and figured out the mechanism to override the system.

“We found specific hormonal signals produced by the old B cells, the memory cells, that inhibit the bone marrow from producing new B cells,” Melamed said. “This is a huge discovery. It is like finding a needle in a haystack.”

It also means that over time specific drugs or treatments could be found to inhibit one of the hormones in the signaling pathway and get the bone marrow to produce new B cells. 

To validate their theory, Melamed’s lab collaborated with the departments of hematology and rheumatology at Tel Aviv Sourasky Medical Center and Rambam Health Care Campus. As part of treatment for some medical conditions, such as lupus, lymphoma, and multiple sclerosis, patients undergo B cell depletion, meaning a significant amount of memory B cells are removed from their bodies. 

Examining older patients who underwent this procedure, the group found their immune systems rejuvenated, and their bodies could produce new B cells again.

An effect similar to B cell depletion can be produced by inhibiting one of the hormones in the signaling pathway that suppresses the production of new B cells.

“Now we understand that there is some kind of conversation between compartments in the body, between how B cells are produced and what controls that,” Melamed said.

In the interim, he recommended that doctors use this knowledge to better protect the elderly, such as by instituting a vaccination program targeted just for the adult population that preempts variants with an additional shot – “even every three or four months, vaccinate them again and again, to ensure they maintain high antibodies.”

Another suggestion he had was to mix vaccines, such as combining a shot of a Pfizer mRNA vaccine with an AstraZeneca booster given several months later, “which may generate better stimulation of the elderly immune system.”

At the same time, he said clinical trials would be needed to determine how to safely inhibit the hormones in order to find a longer-term solution – hopefully before the next pandemic.