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Lookup NU author(s): Dr Patrick Yu Wai Man, Dr Gillian Borthwick, Dr Langping He, Geoffrey Taylor, Professor Laura GreavesORCiD, Professor Robert Taylor, Philip Griffiths, Emeritus Professor Doug Turnbull
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PURPOSE. Mitochondrial function and the presence of somatic mitochondrial DNA (mtDNA) defects were investigated in extraocular muscles (EOMs) collected from individuals covering a wide age range, to document the changes seen with normal aging. METHODS. Cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) histochemistry was performed on 46 EOM samples to determine the level of COX deficiency in serial cryostat muscle sections (mean age, 42.6 years; range, 3.0-96.0 years). Competitive three-primer and real-time PCR were performed on single-fiber lysates to detect and quantify mtDNA deletions. Whole-genome mitochondrial sequencing was also performed to evaluate the contribution of mtDNA point mutations to the overall mutational load. RESULTS. COX-negative fibers were seen in EOMs beginning in the third decade of life, and there was a significant age-related increase: <30 years, 0.05% (n = 17); 30 to 60 years, 1.94% (n = 13); and >60 years, 3.34% (n = 16, P = 0.0001). Higher levels of COX deficiency were also present in EOM than in skeletal muscle in all three age groups (P < 0.0001). Most of the COX-negative fibers harbored high levels (>70%) of mtDNA deletions (206/284, 72.54%) and the mean deletion level was 66.64% (SD 36.45%). The mutational yield from whole mitochondrial genome sequencing was relatively low (1/19, 5.3%), with only a single mtDNA point mutation identified among COX-negative fibers with low deletion levels <= 70%. CONCLUSIONS. The results show an exponential increase in COX deficiency in EOMs beginning in early adulthood, which suggests an accelerated aging process compared with other post-mitotic tissues. (Invest Ophthalmol Vis Sci. 2010; 51:3347-3353) DOI:10.1167/iovs.09-4660
Author(s): Yu Wai Man P, Lai-Cheong J, Borthwick GM, He LP, Taylor GA, Greaves LC, Taylor RW, Griffiths PG, Turnbull DM
Publication type: Article
Publication status: Published
Journal: Investigative Ophthalmology & Visual Science
Year: 2010
Volume: 51
Issue: 7
Pages: 3347-3353
Print publication date: 17/02/2010
ISSN (print): 0146-0404
ISSN (electronic): 1552-5783
Publisher: Association for Research in Vision and Ophthalmology
URL: http://dx.doi.org/10.1167/iovs.09-4660
DOI: 10.1167/iovs.09-4660
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