SYSTEMAGE

Early warning signals of ageing in human stem cells and age-related disorders

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 Obiettivo del progetto (Objective)

'The regenerative power of a living organism is linked to the potential of its stem cells to replace the corresponding damaged tissue. Therefore organisms are as old as their stem cells. Whereas the vulnerability to cancer and chronic inflammation is associated with a decline of the immune system, the latter is in turn a sum product of interactions among hematopoietic stem cells (HSC), endothelial cells (EC) of the vascular systems and the microenvironment in the bone marrow, among others. Hence loss of regenerative function and propensity to contract cancers can be interpreted as harbingers of ageing at the level of somatic stem cells. Using HSC and their microenvironment as a model, our principal goal is to develop a systems-level understanding of the molecular mechanisms of ageing in somatic stem cells, the consequences, and means to correct these age-related alterations and diseases. We intend to apply integrative systems biology approaches to characterize the molecular players, genes and pathways that are associated with physiological processes of ageing and two age-related disorders, myelodysplastic syndromes (MDS) and B-cell chronic lymphocytic leukemia (B-CLL). We will use the resulting models of ageing to develop novel, molecular targeted strategies to treat age-related diseases. The SyStemAge consortium involves three hospital departments that are active in implementing innovative treatment strategies of leukaemia and MDS, a number of biomedical departments engaged with basic research in the processes underlying these diseases, two Systems Biology groups, one of Europe’s most experienced group in biomedical modelling and complex systems theory and two SMEs with proven expertise in the translation of biomedical models in novel therapy strategies in humans. SyStemAge is uniquely positioned to bridge the gap between the clinical, biomedical and natural sciences and immediately contribute to bio-gerontology.'

Introduzione (Teaser)

An international consortium is working to unveil how the regenerative potential of an organism relates to age. The study is anticipated to make interesting discoveries about ageing and develop innovative treatments for age-related disorders.

Descrizione progetto (Article)

Tissue homeostasis and regeneration are two processes governed by a specific sub-population of tissue-resident stem cells. These cells have the capacity to self-renew as well as to differentiate to give rise to most cells in the tissue. This choice is mainly governed by the signal they receive from their immediate environment.

With ageing, the regenerative capacity of these cells is believed to diminish, giving rise to many disorders, including cancer. Cancer and chronic inflammation are associated with a decline in immune system function that, in turn, is regulated through the concerted interaction of hematopoietic stem cells (HSCs) and the bone marrow microenvironment.

The principal goal of the EU-funded 'Early warning signals of ageing in human stem cells and age-related disorders' (http://systemage.eu/ (SYSTEMAGE)) project is to understand the molecular mechanisms of ageing in hematopoietic stem cells. In this context, the partners are using HSCs and their bone marrow microenvironment as a model to investigate the impact of ageing.

As a first step, partners have isolated different bone marrow cell populations from young and elderly individuals and are in the process of analysing them using transcriptomics, proteomics and metabolomics. This information will be utilised to understand the age-related disorders myelodysplastic syndrome (MDS) and B-cell chronic lymphocytic leukaemia (B-CLL), and to define the deregulated pathways.

Another part of the project is dedicated to the development of novel mouse models of ageing. Scientists will determine the epigenetic modifications in cells from young and adult mice, and also use these models to test novel, targeted strategies for the treatment of age-related diseases. Combined, these data will become integrated to generate computational models for the in silico studying of ageing.

Overall, through basic and translational studies, multi-level omics analyses and drug discovery, SYSTEMAGE will provide a global view of the processes involved in physiological and pathological ageing. This is vital for understanding the aetiology behind age-related disorders.