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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access published online on June 5, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, doi:10.1093/gerona/glp070
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© The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Aging-Associated Alteration of Subtelomeric Methylation in Parkinson's Disease

Toyoki Maeda, Jing Zhi Guan, Jun-ichi Oyama, Yoshihiro Higuchi and Naoki Makino

Department of Molecular and Cellular Biology, Division of Molecular and Clinical Gerontology, Medical Institute of Bioregulation, Kyushu University, Oita, Japan

Address correspondence to Toyoki Maeda MD, PhD, Department of Molecular and Cellular Biology, Division of Molecular and Clinical Gerontology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, Oita 874-0838, Japan. Email: maedat{at}beppu.kyushu-u.ac.jp


  Abstract

A telomere is a repetitive DNA structure capping the chromosomal ends. Telomeres stabilize the chromosome structure and prevent harmful end-to-end recombinations. The telomere length of somatic cells can be determined as the terminal restriction fragment length provided by a genomic Southern blotting analysis, and the telomere length becomes shorter at each mitotic cycle due to an "end-replication problem." Therefore, older somatic cells, which have undergone more mitotic cycles, bear shorter telomeres. This telomere shortening is accelerated by various disease conditions. Parkinson’s disease (PD) also yields telomere fragility, thus accelerating the telomere shortening of the circulating leukocytes. This study found that peripheral leukocytes of Japanese PD patients bear fewer short telomeres with constant subtelomeric methylation status in comparison with the healthy controls with increasing short telomeres and also increasing hypomethylated subtelomeres in short telomeres with aging. The correlation between the telomeric attrition and the subtelomeric methylated state in PD is herein discussed.

Keywords Subtelomere; Aging; DNA methylation; Parkinson's disease; Japanese

Received: September 1, 2008; Accepted: January 12, 2009

Decision Editor: Huber R. Warner, PhD


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