title: Age-associated mitochondrial DNA mutations lead to small but significant changes in cell proliferation and apoptosis in human colonic crypts.
abstract: Mitochondrial DNA (mtDNA) mutations are a cause of human disease and are proposed to have a role in human aging. Clonally expanded mtDNA point mutations have been detected in replicating tissues and have been shown to cause respiratory chain (RC) defects. The effect of these mutations on other cellular functions has not been established. Here, we investigate the consequences of RC deficiency on human colonic epithelial stem cells and their progeny in elderly individuals. We show for the first time in aging human tissue that RC deficiency attenuates cell proliferation and increases apoptosis in the progeny of RC deficient stem cells, leading to decreased crypt cell population.
authors.affiliation: Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Nooteboom
authors.forename: Riem
authors.initials: R
authors.lastname: Johnson
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Wright
authors.forename: Robert N
authors.initials: RN
authors.lastname: Lightowlers
authors.forename: Thomas B L
authors.initials: TB
authors.lastname: Kirkwood
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
authors.forename: Doug M
authors.initials: DM
authors.lastname: Turnbull
authors.forename: Laura C
authors.initials: LC
authors.lastname: Greaves
mesh_terms: D000375:Aging; D017209:Apoptosis; D049109:Cell Proliferation; D003106:Colon / Q000166:cytology* / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D009154:Mutation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D019394:Ki-67 Antigen; D003576:Electron Transport Complex IV