EU-funded project investigates molecular mechanisms of aging in adult stem cells

Stem cells are the ultimate mother cells of the human body. Not only do they have the capacity to self-renew, they can develop into specific cell types as the body requires. But as the human body ages, the regenerative capacity of our stem cells diminishes. For example, as the capacity of hematopoietic stem cells (HSCs) to regenerate other blood cells diminishes, so does our immune system, thus giving rise to such disorders as cancer.

To better understand – and treat – such age-related disorders as cancer, researchers with the EU-funded SyStemAge project studied HSC aging within the red bone marrow microenvironment. “Because vulnerability to cancer is associated with a decline in the immune system, a loss in the regenerative function of our stem cells can be interpreted as an early warning sign for the propensity to contract cancer,” explains Adndrey Zaritskey, a leading researcher at Russia’s Almazov Medical Research Centre, one of the SyStemAge project’s partners. “Using HSC and their microenvironment as a model, our goal was to develop a systems-level understanding of the molecular mechanisms of ageing in adult stem cells, the consequences of this aging and a means to correct age-related alterations and diseases.”

Expertise in B-CLL

Being a centre of excellence in B-chronic lymphocytic leukemia (B-CLL), a type of cancer of the blood and bone marrow, the Haematology Institute at Almazov Medical Research Centre was well-positioned to provide the project with important insights from its B-CLL patients.

“With scientific research being a key part of our medical center, we were able to study HSCs across a variety of patients and age groups,” explains Zaritskey. “Furthermore, our state-of-the-art facilities and biobank have enabled us to readily isolate, sort and store biological material before sending it to the European Molecular Biology Laboratory, or EMBL, for further validation.”

Benefits all around

Thanks in part to the Almazov Medical Research Centre’s expertise in the clinical and fundamental aspects of B-CLL, the SYSTEMAGE project was able to translate knowledge about HSC aging into potential new treatments. For example, researchers standardized and harmonized methods for isolating HSC, mesenchymal stroma cells (MSC) and other constituent cells of the bone marrow niche from healthy human subjects, as well as from patients with B-CLL. “In close collaboration, we compared the differences in the mechanisms of physiological aging versus those with B-CLL,” adds Zaritskey.

The Almazov Medical Research Centre also benefited from its collaboration on the project. “The results of the project laid the foundation for the ongoing clinical research that we are conducting here at the Centre,” says Zaritskey. “It also opened the door to a continuing collaboration with Kyoto University.”

But most importantly, it is the general public that will benefit from the project’s work. “The main basis of our health is the state of our immune system, which is maintained by HSC,” adds Zaritskey. “What we learned is that although aging may have many facets, keeping our blood cells healthy benefits all our body’s systems – leading to a happier, healthier and longer life.”