Rhosin shown to reverse blood stem cell ageing

Researchers at IDIBELL-Bellvitge Biomedical Research Institute in Barcelona have announced a potential strategy to slow or even reverse aspects of biological ageing by targeting blood stem cells. This discovery could one day extend healthy lifespans and reduce the burden of age-related disease. The findings build on previous work by Dr M. Carolina Florian and her team, who demonstrated the importance of the haematopoietic system in driving whole-body ageing.

Their latest study identifies the molecule Rhosin, a drug capable of inhibiting the protein RhoA, which becomes highly activated as blood stem cells age. By dampening this activity, scientists successfully rejuvenated aged stem cells in laboratory and animal models.

Targeting ageing at its core

Ageing is a gradual decline in function over time and is a major risk factor for numerous chronic conditions. While it affects the entire body, researchers have long known that deterioration within the haematopoietic system alone can influence whole-body health. Blood stem cells – formally known as haematopoietic stem cells – live in the bone marrow and continually generate vital blood components, from oxygen-carrying red blood cells to immune-regulating white blood cells.

Overall, our experiments show that Rhosin did rejuvenate blood stem cells, increased the regenerative capacity of the immune system and improved the production of blood cells once transplanted in the bone marrow.

With age, these cells lose their ability to regenerate effectively. They produce fewer, less functional immune cells, contributing to immunosenescence, persistent low-grade inflammation and a rise in chronic disease.

At the cellular level, repeated replication leads to the accumulation of mutations and the loss of key epigenetic markers. This disrupts DNA organisation inside the nucleus and increases mechanical stress on the nuclear envelope which activates RhoA – a mechanosensor that plays a key role in the ageing of blood stem cells.

The team demonstrated that inhibiting RhoA with the drug Rhosin reversed many of these age-associated changes. Dr Eva Mejía-Ramírez, researcher at IDIBELL and co-author of the study, said: “Overall, our experiments show that Rhosin did rejuvenate blood stem cells, increased the regenerative capacity of the immune system and improved the production of blood cells once transplanted in the bone marrow.”

Experiments were conducted both in vivo and in vitro at IDIBELL. Meanwhile, collaborators at ISGlobal and the Barcelona Supercomputing Center applied machine-learning techniques to discover how Rhosin remodels chromatin within the treated cells.

A growing ageing crisis

By 2050, the population of people over 60 in Western countries is expected to double compared with 2015, dramatically increasing cases of cancer, dementia and cardiovascular disease. With ageing set to place real strain on healthcare and social-care systems, identifying treatments that address the biological causes of ageing has become a priority.

With ageing set to place real strain on healthcare and social-care systems, identifying treatments that address the biological causes of ageing has become a priority.

Although lifestyle interventions and some drugs show potential anti-ageing effects, Dr Florian stresses their limits: “These measures cannot be qualified as rejuvenation because they combat the effects of ageing rather than acting on the process itself. In contrast, we target the core of the ageing process: by reverting blood stem cells to a younger state, we make them more capable of regenerating and producing new healthy blood cells, which improves the health of the whole organism. This is why we talk about cell rejuvenation."

Next steps towards human application

While results in animal models are encouraging, clinical research is needed to determine whether Rhosin can safely and effectively rejuvenate blood stem cells in humans. To protect and advance the work, Dr Florian has worked with the IDIBELL Innovation Unit to submit the findings for a European patent – an important step toward potential future commercialisation and safeguarding against misuse by third parties.

Researchers remain optimistic that these early breakthroughs could move us closer to therapies that can enhance the quality of life for ageing populations.