title: Aging-Induced Stem Cell Mutations as Drivers for Disease and Cancer.
abstract: Aging is characterized by a decrease in genome integrity, impaired organ maintenance, and an increased risk of cancer, which coincide with clonal dominance of expanded mutant stem and progenitor cell populations in aging tissues, such as the intestinal epithelium, the hematopoietic system, and the male germline. Here we discuss possible explanations for age-associated increases in the initiation and/or progression of mutant stem/progenitor clones and highlight the roles of stem cell quiescence, replication-associated DNA damage, telomere shortening, epigenetic alterations, and metabolic challenges as determinants of stem cell mutations and clonal dominance in aging.
authors.affiliation: University of Glasgow and Beatson Institute for Cancer Research, Glasgow G61 1BD, UK.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Adams
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Jasper
authors.affiliation: Leibniz Institute for Age Research - Fritz Lipmann Institute e.V. (FLI), Beutenbergstr. 11, 07745 Jena, Germany. Electronic address: KLRudolph@FLI-Leibniz.de.
authors.forename: K Lenhard
authors.initials: KL
authors.lastname: Rudolph
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D044127:Epigenesis, Genetic; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism*; D059506:Telomere Shortening