Understanding epigenetic changes in aging stem cells – a computational model approach

摘要: During aging, a decline in stem cell function is observed many tissues. This accompanied by complex changes of the chromatin structure among them histone modifications and DNA methylation which both affect transcription tissue-specific subset genes. A mechanistic understanding these age-associated processes, their interrelations environmental dependence currently lacking. Here, we discuss related questions on molecular, cellular, population level. We combine an individual cell-based model populations with epigenetic regulation transcription. The novel enables to simulate age-related trimethylation lysine 4 at H3 methylation. These entail expression genes that induce phenotypes (ARPs) cells. compare regulatory states quiescent cells occupying niche those proliferating Moreover, analyze impact activity involved modifiers changes. find aging strongly affects heterogeneity homing niches retards aging. Our provides explanation how increased proliferation can lead progeroid phenotypes. Adapting our properties for aged hematopoietic (HSC) clones, predict ARP activates young HSCs thereby entire HSC population. In addition, suggests experimentally high interindividual variance numbers originates methyltransferase activity.