Journal
EXPERIMENTAL GERONTOLOGY
Volume 45, Issue 7-8, Pages 573-579Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2010.01.013
Keywords
Ageing; Mitochondria; mtDNA; Colon; Respiratory chain; Mutation
Categories
Funding
- Biotechnology and Biological Sciences Research Council [BB/C008200/1] Funding Source: researchfish
- Medical Research Council [G0900686, G0601333, G0601943, G0800674] Funding Source: researchfish
- MRC [G0601333, G0601943, G0900686, G0800674] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/C008200/1] Funding Source: Medline
- Medical Research Council [G0800674, G0900686, G0601943, G0601333] Funding Source: Medline
- Wellcome Trust [074454] Funding Source: Medline
Ask authors/readers for more resources
Mitochondrial DNA (mtDNA) mutations accumulate in a number of ageing tissues and are proposed to play a role in the ageing process. We have previously shown that colonic crypt stem cells accumulate somatic mtDNA point mutations during ageing. These mtDNA mutations result in the loss of the activity of complex IV (cytochrome c oxidase (COX)) of the respiratory chain in the stem cells and their progeny, producing colonic crypts which are entirely COX deficient. However it is not known whether the other complexes of the respiratory chain are similarly affected during ageing. Here we have used antibodies to individual subunits of complexes I-IV to investigate their expression in the colonic epithelium from human subjects aged 18-84. We show that in similar to 50% of crypts with any form of respiratory chain deficiency, decreased expression of subunits of multiple complexes is observed. Furthermore we have sequenced the entire mitochondrial genome of a number of cells with multiple complex defects and have found a wide variety of point mutations in these cells affecting a number of different protein encoding and RNA encoding genes. Finally we discuss the possible mechanisms by which multiple respiratory chain complex defects may occur in these cells. (C) 2010 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available