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Introduction - concept - objectives

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, the principal goal of SyStemAge 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.

Concept

The project intends 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 leukaemia (B-CLL). The resulting models of ageing will be used to develop novel, molecular targeted strategies to treat age-related diseases.

Objectives

Specifically, the missions of SyStemAge are:

  1. To define the fundamental molecular and cell biological mechanisms of ageing in models of somatic stem cells, in order to comprehend the roles of genetic and proteomics alterations on the process of ageing
  2. To determine the molecular and cellular alterations of HSC and other cellular determinants that constitute the marrow niche (e.g. MSC, macrophages and lymphocytes) with ageing, and the impact of ageing of these cellular determinants on their respective supportive function for HSC
  3. To combine the cell biological, “-omics” and genetic studies to build models of age-related diseases such as myelodysplastic syndromes (MDS) and B-cell chronic lymphocytic leukaemia (B-CLL)
  4. To translate the systems understanding of stem cell ageing into novel drug discovery strategies.

Mesenchymal stromal cells.

Consortium

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 groups in biomedical modeling and complex systems theory and two SMEs with proven expertise in the translation of biomedical models into novel therapy strategies in humans.

SyStemAge is uniquely positioned to brigde the gap between the clinical, biomedical and natural sciences and immediately contribute to bio-gerentology.