contributed equally to this work.
Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: mitochondrial DNA (mtDNA); ribosomal RNA (rRNA); transfer RNA (tRNA); succinate dehydrogenase (SDH).
contributed equally to this work.
Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: mitochondrial DNA (mtDNA); ribosomal RNA (rRNA); transfer RNA (tRNA); succinate dehydrogenase (SDH).
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 ∼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.
Anal sphincter pressures, rectal compliance and sensation in 19 women of mean age 77 (range 57-94) years were studied before and after Delorme's procedure for full-thickness rectal prolapse. No patient had significant problems with defaecation after operation. There were no significant changes in anal sphincter pressures but the volume of first rectal sensation decreased from a median of 140 ml before surgery to 65 ml after the procedure (P = 0.01) and the maximum tolerated rectal volume declined from a median of 249 ml to 120 ml (P = 0.001). Rectal compliance was reduced from a median of 142.9 ml/kPa to 12.2 ml/kPa (P = 0.002). Improved rectal sensation and lowered compliance are associated with a reduced incidence of defaecatory problems after Delorme's procedure.
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