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. 2010 Feb;9(1):96-9.
doi: 10.1111/j.1474-9726.2009.00531.x. Epub 2009 Oct 30.

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

Marco Nooteboom  1 , Riem Johnson, Robert W Taylor, Nicholas A Wright, Robert N Lightowlers, Thomas B L Kirkwood, John C Mathers, Doug M Turnbull, Laura C Greaves
Affiliations

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

Marco Nooteboom et al. Aging Cell. 2010 Feb.

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.

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Figures

Fig. 1
Fig. 1
Dual immunofluorescence investigating the functional effects of respiratory chain (RC) deficiency. RC function is detected by expression of cytochrome c oxidase (COX) subunit I. (A) Expression of Ki-67 (red) and COX subunit I (green). A RC deficient crypt is shown in this image. (B) Frequency of actively proliferating cells in RC normal and deficient crypts ± SD. The numbers of each type of crypt analysed for each subject were: subject 1, age 79, 15 normal, five deficient; subject 2, age 89, 15 normal, 14 deficient; subject 3, age 84, 13 normal six deficient; subject 4, age 73, 15 normal, 13 deficient; subject 5, age 85, 15 normal, eight deficient; subject 6, age 75, 15 normal, ten deficient. Panel C shows a RC deficient hemi-crypt to illustrate nuclei counting to determine crypt length. (D) Expression of M30 CytoDeath (red) and COX subunit I (green), the white arrows highlight apoptotic cells. (E) Crypt cell population based on the crypt length multiplied by the average crypt circumference of the RC normal and RC deficient crypts for each subject. Subjects and numbers of crypts; same as for Ki-67 analysis. Error bars are the SEM of the products. (F) Expression of β-catenin (red) and COX subunit I (green). β-catenin was detected in the cytoplasm of both RC normal (white arrow) and RC deficient crypts (red arrow). Scale bars 20 μm.
See this image and copyright information in PMC

References

    1. Fearnhead NS, Britton MP, Bodmer WF. The ABC of APC. Hum. Mol. Genet. 2001;10:721–733. - PubMed
    1. Fellous TG, Islam S, Tadrous PJ, Elia G, Kocher HM, Bhattacharya S, Mears L, Turnbull DM, Taylor RW, Greaves LC, Chinnery PF, Taylor G, McDonald SA, Wright NA, Alison MR. Locating the stem cell niche and tracing hepatocyte lineages in human liver. Hepatology. 2009a;49:1655–1663. - PubMed
    1. Fellous TG, McDonald SA, Burkert J, Humphries A, Islam S, De-Alwis NM, Gutierrez-Gonzalez L, Tadrous PJ, Elia G, Kocher HM, Bhattacharya S, Mears L, El-Bahrawy M, Turnbull DM, Taylor RW, Greaves LC, Chinnery PF, Day CP, Wright NA, Alison MR. A methodological approach to tracing cell lineage in human epithelial tissues. Stem Cells. 2009b;27:1410–1420. - PubMed
    1. Goodlad RA, Mandir N, Levin S, Allen JL, Wright NA. Prostaglandins and the colonic epithelium. Effects of misoprostol on crypt size, cell production, and cell migration in the dog. Gastroenterology. 1991;101:1229–1234. - PubMed
    1. Kirkwood TB. A systematic look at an old problem. Nature. 2008;451:644–647. - PubMed

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