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Age-associated mitochondrial DNA mutations lead to small but significant changes in cell proliferation and apoptosis in human colonic crypts

Lookup NU author(s): Marco Nooteboom, Professor Robert Taylor, Professor Robert Lightowlers, Emeritus Professor Thomas Kirkwood, Professor John Mathers, Emeritus Professor Doug Turnbull, Dr Laura Greaves



P>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.

Publication metadata

Author(s): Nooteboom M, Johnson R, Taylor RW, Wright NA, Lightowlers RN, Kirkwood TBL, Mathers JC, Turnbull DM, Greaves LC

Publication type: Article

Publication status: Published

Journal: Aging Cell

Year: 2010

Volume: 9

Issue: 1

Pages: 96-99

Print publication date: 01/02/2010

Date deposited: 27/05/2010

ISSN (print): 1474-9718

ISSN (electronic): 1474-9726

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/j.1474-9726.2009.00531.x


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Funder referenceFunder name
Cancer Research UK
Wellcome Trust
Biotechnology and Biological Sciences Research Council
Medical Research Council
074454Wellcome Trust
BB/C008200/1Biotechnology and Biological Sciences Research Council
G0700718Medical Research Council