Ageing, defined as the deterioration of the body’s function and structure over time, is one of the main risk factors for numerous chronic diseases. Although it is a complex phenomenon affecting the whole organism, ageing of the haematopoietic system is one of its main drivers. Last September, the IDIBELL and ICREA researcher Dr. M. Carolina Florian and her research group underlined the relevance of using blood stem cells to pharmacologically target ageing of the whole body. They also suggested rejuvenating strategies that could extend healthspan and lifespan. Now, in a Nature Aging publication, the research group discovered the rejuvenating potential of the drug Rhosin on blood stem cells.
This study was based on the collaboration between Dr. Florian’s team at IDIBELL, where the in vivo and in vitro assays took place, and innovative in silico machine learning techniques by Dr Paula Petrone at the Barcelona Institute for Global Health (ISGlobal), a centre supported by the ”la Caixa” Foundation, and the Barcelona Supercomputing Center-Centro Nacional de Supercomputación (BSC-CNS).
Acting on the heart of the aging process: the nucleus of blood stem cells
Blood stem cells, or hematopoietic stem cells, are located in the bone marrow and are responsible for the vital function of continuously producing all types of blood cells (oxygen transporters, immune cells and platelets). Over time, however, stem cells also do age, they lose their regenerative capacity and generate less and lower-quality cells. Their ageing has been linked to immunosenescence, chronic low-grade inflammation, several aging-related chronic diseases and cancer.
In the cell nuclei, the effects of ageing are evidenced by the accumulation of mutations and the loss of DNA organisation inside the nucleus, which builds up mechanical tension and hinder DNA replication.
This study revealed the rejuvenating potential of RhoA in blood stem cells. After figuring out the key role of this protein in the cell ageing process, researchers proved their potential as a pharmacological target for rejuvenation. First, they treated aged blood stem cells ex vivo with Rhosin, a RhoA inhibitor, and they observed how these cells returned to a younger state. As IDIBELL researcher and study co-first author Dr Eva Mejía-Ramírez summarizes: “Overall, our experiments show that Rhosin rejuvenates blood stem cells, increases the immune system regenerative capacity and enhances blood cell production once transplanted into the bone marrow.” The in vitro and in vivo assays were conducted entirely in IDIBELL by the stem cell ageing research group, lead by Dr Florian. Pablo Iáñez-Picazo, “La Caixa” Foundation fellow, and Dr Paula Petrone, from the ISGlobal and the BSC-CNS, used innovative computer vision and machine learning approaches to characterize DNA organization. This project also relies on a long-term collaboration with Prof. Yi Zheng at CCHMC (USA), who had previously developed and validated the Rhosin molecule.
The ageing of society: a not-so-far future health problem
In 2050, the population over 60 years in Western countries will have doubled compared to 2015, leading to an associated increase in the incidence of many chronic diseases such as cancer, dementia and cardiovascular conditions. This will place a major burden on all countries health and social systems. Designing treatments that relieve the negative effects of ageing on health is vital, and they should be based on quality biomedical research, regardless of aesthetic or cosmetic aspects. There is positive evidence on certain lifestyle changes and medications that may qualify as anti-ageing, together with some research lines at a molecular level. However, according to Dr. Florian, “These measures cannot be qualified as rejuvenation because they combat the effects of ageing rather than acting on the process itself. We instead revert blood stem cells to a younger state and make them capable of producing healthier blood cells, ultimately aiming to improve overall health. This is why we talk about stem cell rejuvenation“.
Results are promising and researchers feel very optimistic about how this new strategy might improve the quality of life of the elderly. Now, clinical research must verify whether the results in animal models can be safely and effectively translated to humans. In this line, Dr Florian counted on the IDIBELL Innovation Unit to submit the results for a European patent and to help in translating her findings to clinical applications.
About IDIBELL
The Bellvitge Biomedical Research Institute (IDIBELL) is a research center established in 2004 specialized in cancer, neuroscience, translational medicine, and regenerative medicine. It counts on a team of more than 1.500 professionals who, from 73 research groups, publish more than 1.400 scientific articles per year. IDIBELL is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona, and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).
About ISGlobal
The Barcelona Institute for Global Health, ISGlobal, is the fruit of an innovative alliance between the ”la Caixa” Foundation and academic and government institutions to contribute to the efforts undertaken by the international community to address the challenges in global health. ISGlobal is a consolidated hub of excellence in research that has grown out of work first started in the world of health care by the Hospital Clínic and the Hospital del Mar and in the academic sphere by the University of Barcelona and Pompeu Fabra University. Its working model is based on the generation of scientific knowledge through Research Programmes and Groups, and its translation through the areas of Training and Analysis and Global Development. ISGlobal has been named a Severo Ochoa Centre of Excellence and is a member of the CERCA system of the Generalitat de Catalunya.
About BSC
Barcelona Supercomputing Center is one of the leading supercomputing centers in Europe and hosts one of the most powerful supercomputers in the world, MareNostrum 5. BSC specialises in High Performance Computing (HPC) and has a dual mission: to provide supercomputing infrastructure and services to the Spanish and European scientific communities, and to generate knowledge and technology for transfer to society. The BSC consortium is made up of the Ministry of Science, Innovation and Universities of the Government of Spain (60%), the Department of Research and Universities of the Government of Catalonia (30%) and the Polytechnic University of Catalonia (10%). The centre manages the Spanish Supercomputing Network (RES) and is one of the hosting entities of the EuroHPC JU, the initiative leading large-scale investment and deployment of HPC in Europe.
- Read the article in Nature Aging here
- Download the original press release here
- Read Maria Carolina Florian’s EATRIS Meets here
- Learn more about EATRIS institute IDIBELL
- Learn more about EATRIS Spain
