Toggle Main Menu Toggle Search

Open Access padlockePrints

Somatic Mitochondrial DNA Deletions Accumulate to High Levels in Aging Human Extraocular Muscles

Lookup NU author(s): Dr Patrick Yu Wai Man, Dr Gillian Borthwick, Dr Langping He, Geoffrey Taylor, Dr Laura Greaves, Professor Robert Taylor, Philip Griffiths, Professor Doug Turnbull

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

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


Publication metadata

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


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share