title: Genome instability of ageing stem cells--Induction and defence mechanisms.
abstract: The mammalian organism is comprised of tissue types with varying degrees of self-renewal and regenerative capacity. In most organs self-renewing tissue-specific stem and progenitor cells contribute to organ maintenance, and it is vital to maintain a functional stem cell pool to preserve organ homeostasis. Various conditions like tissue injury, stress responses, and regeneration challenge the stem cell pool to re-establish homeostasis (Fig. 1). However, with increasing age the functionality of adult stem cells declines and genomic mutations accumulate. These defects affect different cellular response pathways and lead to impairments in regeneration, stress tolerance, and organ function as well as to an increased risk for the development of ageing associated diseases and cancer. Maintenance of the genome appears to be of utmost importance to preserve stem cell function and to reduce the risk of ageing associated dysfunctions and pathologies. In this review, we discuss the causal link between stem cell dysfunction and DNA damage accrual, different strategies how stem cells maintain genome integrity, and how these processes are affected during ageing.
authors: Leibniz Institute for Age Research, Fritz-Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany. Electronic address: mburkhalter@fli-leibniz.de.
authors: Martin D
authors: MD
authors: Burkhalter
authors: Leibniz Institute for Age Research, Fritz-Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany.
authors: K Lenhard
authors: KL
authors: Rudolph
authors: Leibniz Institute for Age Research, Fritz-Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany. Electronic address: tsperka@fli-leibniz.de.
authors: Tobias
authors: T
authors: Sperka
mesh_terms: D000818:Animals; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology*; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D004260:DNA Repair / Q000235:genetics / Q000502:physiology; D042822:Genomic Instability / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D009154:Mutation / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*
keywords: Ageing; Cancer; Checkpoint; DNA repair; Genome maintenance; Stem cell