Stem Cell Aging

Our research focuses on epi-/genetic and molecular mechanisms of stem cell aging. Adult tissue stem cells have a pivotal role in lifelong maintenance of organ homeostasis and regeneration in response to injury. There is experimental and clinical evidence that the functional capacity of stem cells declines during aging. Stem cell aging involves cell intrinsic accumulation of molecular damages as well as stem cell extrinsic alteration in stem cell niches and in the blood circulation. Causal mechanisms underlying these alterations in stem cells and the stem cell environment as well as its consequences for organism aging (and vice versa) remain incompletely understood. In the last 5 years, research work of our group was mainly focused on three areas of stem cell aging:

• Molecular damages and checkpoint/quality control pathways
• Systemic factors, metabolism and inflammation
• Epi-/genetic factors and clonal selection

Our research in these three areas is connected at multiple levels: Molecular damages impinge on the regulation of metabolic pathways. Vice versa metabolites influence the accumulation of molecular damages. Aging-associated accumulation of molecular damages, such as DNA damage, as well as changes in metabolic pathways contribute to changes in the epigenome in aging stem cells. Aging-associated epigenetic alteration in turn lead to aberrant regulation of developmental pathways altering stem cell function. The main aim of our research is to delineate mechanisms and interactions between epi-/genetic, metabolic, and molecule mechanisms of stem cell aging.