Aging-associated alteration of subtelomeric methylation in Parkinson's disease

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. Key Words: Subtelomere--Aging--DNA methylation--Parkinson's disease--Japanese.