Aging-Associated Alteration of Telomere Length and Subtelomeric Status in Female Patients With Parkinson's Disease

Abstract

Abstract: A telomere is a repetitive DNA structure at chromosomal ends that stabilizes the chromosome structure and prevents harmful end-to-end recombinations. The telomere length of somatic cells becomes shorter with aging because of the “end replication problem.” This telomere shortening is accelerated by pathophysiological conditions including daily mental stress. Living with Parkinson's disease (PD) causes physical and mental stress; therefore, the authors hypothesized that the telomere length of somatic cells was shortened excessively in patients with PD. In order to detect PD-associated somatic telomeric alterations, the telomere length and subtelomeric methylation status of peripheral leukocytes of PD patients were assessed by Southern blotting, using methylation-sensitive and -insensitive isoschizomers. The results demonstrated that the peripheral leukocytes of Japanese female patients with PD bore fewer long telomeres and a proportional increase of hypomethylated subtelomeres in short telomeres in comparison with the healthy controls. This study indicates that with the neurodegeneration associated with PD, telomeric and subtelomeric structural alterations occur. These structural telomere altertions most likely occur secondary to the acceleration of aging-associated telomeric changes and the accelerated loss of cells bearing short telomeres.

Keywords::

• DNA methylation
• Parkinson's disease
• telomere
• subtelomere

ACKNOWLEDGMENTS

This work was supported by grants from the Ministry of Education, Science, and Culture of Japan (no. 23590885) and the National Natural Science Fund (NSFC) (no. 81170329/H2501). The authors thank Ms. Ueda and Ms. Taguchi for their valuable technical assistance. The authors are also grateful to Mr. Brian Quinn for his linguistic advice on the manuscript.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.