August 10, 2021

Why are the Elderly at Risk?

Why are the Elderly at Risk?

Technion researchers delve into the aging of the immune system and the means of reversing this process

Professor Doron Melamed (right) and Dr. Reem Dowery

The elderly population appears to be more vulnerable to COVID-19, and vaccines are less effective in protecting them. Why? In her doctoral thesis under the guidance of Professor Doron Melamed, Reem Dowery discovers the answer, explores the aging process of the immune system, and presents means of rejuvenating it. The findings are now published in Blood.

Memory B lymphocytes are cells within the human body that are responsible for long-term production of effective antibodies. They are formed when the body is exposed to a new pathogen (i.e. virus, microbe, etc.). Upon consequent exposures to the same pathogen, they recognise it and elicit an enhanced antibody response to trigger an accelerated and augmented immunity. These cells are long-lived, capable of surviving and maintaining immune memory for many years. They are what vaccines attempt to generate, providing the body with a first exposure to what it interprets as the pathogen.

It has been known for some time that the formation of memory B lymphocytes is not as effective in the elderly population, putting them at greater risk when facing new pathogens such as COVID-19. Now, for the first time the research group of Prof. Doron Melamed of the Technion’s Ruth and Bruce Rappaport Faculty of Medicine were able to explain why this is so. The group found that as with many other systems in the body, the immune system maintains a steady-state, homeostasis. It turns out that existing memory B lymphocytes, by means of hormonal signals, impede the production of new ones. As a result, with age the human immune system becomes more adept in responding to pathogens it had encountered before, but less capable of adapting to new threats. The same process makes vaccines less effective in protecting the elderly population.

Melamed Research group

With the explanation found, and the signaling pathway through which the phenomenon occurs explained, the researchers wondered, could it be possible to alter, to rejuvenate the immune system? To answer that question, Prof. Melamed’s lab collaborated with the departments of haematology and rheumatology in the Sourasky Medical Centre and the Rambam Health Care Centre, respectively. As part of treatment for some medical conditions (among them lupus, lymphoma, and multiple sclerosis), patients undergo B-cell depletion. In other words, a significant amount of memory B lymphocytes are removed from their body. Examining aged patients who underwent this procedure, the group found their immune system rejuvenated, and their body able to produce new high potent B lymphocytes once again.

An effect similar to B-cell depletion can be produced by inhibiting one of the hormones in the signalling pathway that supresses the production of new memory B lymphocytes. This ground-breaking proof-of-concept study of Reem Dowery and Prof. Melamed has opened the way for exploring the rejuvenation of the immune system. Its more immediate implications are on understanding the immune response in elderly population and providing the correct disease-preventive measures in light of this new information, in particular with regard to the current COVID-19 epidemic.

Click here for the paper in Blood