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Age-associated mitochondrial DNA mutations lead to small but significant changes in cell proliferation and apoptosis in human colonic crypts |
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| Authors: | Marco Nooteboom Riem Johnson Robert W. Taylor Nicholas A. Wright Robert N. Lightowlers Thomas B. L. Kirkwood John C. Mathers Doug M. Turnbull Laura C. Greaves |
| Affiliation: | Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Histopathology Lab, London Research Institute, CRUK London and Barts and the London, UK; Henry Wellcome Laboratory for Biogerontology Research, Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK; Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK |
| 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. |
| Keywords: | aging colon mitochondrial DNA respiratory chain stem cells |