Age-associated mitochondrial DNA mutations lead to small but significant changes in cell proliferation and apoptosis in human colonic crypts.
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.
Nooteboom
Marco
M
Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Johnson
Riem
R
Taylor
Robert W
RW
Wright
Nicholas A
NA
Lightowlers
Robert N
RN
Kirkwood
Thomas B L
TB
Mathers
John C
JC
Turnbull
Doug M
DM
Greaves
Laura C
LC
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
D004272:DNA, Mitochondrial; D019394:Ki-67 Antigen; D003576:Electron Transport Complex IV