Aging and metabolism in tissue maintenance and stem cell function

The age-associated progressive degeneration of many tissues is thought to be driven by the functional decline and gradual attrition of adult stem cells. Within the blood system, anemia of ageing is characterized by peripheral blood cytopenias, bone marrow aplasia and decreased engraftment capacity upon transplantation, indicating impaired hematopoietic stem cells function. The likelihood of developing hematologic malignancies also dramatically increases with age and is potentially driven by HSC dysfunction. The adult brain contains neural stem cells involved in memory formation, consolidation and retrieval, and brain repair. With age the number of neural stem cells decays bringing along memory and regeneration impairments and increased risk of tumor initiation. Skeletal muscle mass and function decline with age (sarcopenia), linked to progressive reduction in regenerative capacity of skeletal muscle stem cells (satellite cells). Groups from the consortium will work on better understanding stem cell function and dysfunction with age.

Specifically, we will explore:

• How the metabolism of stem cells affects aging
• How protein folding and quality control affect tissue homeostasis
• Which signaling pathways in stem cells affects their maintenance and function