A Percentage Analysis of the Telomere Length in Parkinson’s Disease Patients Jing Zhi Guan, 1 Toyoki Maeda, 1 Masahiro Sugano, 1 Jun-ichi Oyama, 1 Yoshihiro Higuchi, 1 Tomokazu Suzuki, 2 and Naoki Makino 1 1 Division of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology and 2 Division of Clinical Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. Telomeres are the repeated sequences at the chromosome ends which undergo shortening with cell division. The telomere shortening of the peripheral leukocytes is also facilitated by enhanced oxidative stress in various kinds of disease including ischemic heart disease, diabetes mellitus, apoplexy, and Alzheimer’s disease. Telomere shortening in Parkinson’s disease (PD) has not yet been reported. The pathogenesis for PD is also regarded to be associated with oxidative stress. We investigated 28 Japanese male PD patients ages 47–69. Although we could not find a statistical difference in the mean telomere length of peripheral leukocytes between the PD patients and the control participants, we found the mean telomere lengths to be shorter than 5 kb in only the PD patients and a significant PD-associated decrease in the telomeres with a length ranging from 23.1 to 9.4 kb in the patients in their 50s and 60s. These observations suggest that telomere shortening is accelerated in PD patients in comparison to the normal population. Key Words: Telomere—Parkinson’s disease—Aging—Oxidative stress—Cell senescence. T ELOMERES are the extreme ends of chromosomal DNA, and they are involved in maintaining cellular stability (1,2). They become progressively shorter after repeated cell division because the DNA polymerase cannot fully complete the replication of the 39 end of linear DNA (3), so the telomere shortening has been regarded to represent cellular aging. Moreover, the mean telomere length of peripheral leukocytes becomes shorter with aging (3–5). This telomere shortening of peripheral leukocytes indicates that the telomere can be a tool to evaluate not only cellular aging but also systemic aging. Recently, the telomere length in peripheral blood cells has been used as the primary model in attempts to decipher links among aging, age-related disorders, and telomere dynamics in humans (6). Acceleration of telomere shortening in peripheral blood cells of people with an age-related disease has been suggested to be related to increased systemic oxidative stress and chronic inflammation in the disease condition (6,7). It was suggested that terminal restriction fragment (TRF) measurement in easily accessible specimens such as peripheral blood could serve as a surrogate parameter for the relative telomere length in other tissues (8), and peripheral blood leukocytes are an excellent source for investigating how telomeres shorten (9). Therefore, telomere shortening in peripheral blood leukocytes can serve not only as a marker of aging but as that of the accumulated oxidative stress and chronic inflammation, which can be an indicator of systemic pathological stress accompanying disease conditions (10). For example, the mean leukocyte TRF length in myocardial infarction patients was significantly shorter than that of the controls and increased the risk of myocardial infarction by approx- imately 3-fold (11). Similarly, the telomeres of endothelial cells associated with coronary atherosclerosis were mark- edly shortened, suggesting that they may play a pathogenic role in coronary arterial diseases (12). Pathophysiological telomere shortening in peripheral blood cells has been also reported in other various pathological conditions (including diabetes mellitus, Alz- heimer’s disease, smoking, and obesity) and in mothers with a high degree of psychological stress related to child care for ill children (13–16). Under these conditions, it is suggested that telomere erosion-inducing factors including oxidative stress and accelerated cell turnover are associated with pathogenesis of the pathological conditions. Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by a progressive degeneration of dopamine-containing neurons. The oxidative stress hypoth- esis (17) and chronic inflammation on the dopaminergic cells of the substantia nigra (18) have been supported by previous studies (19–21). A number of therapies targeting inflammation and mitochondrial dysfunction, which can be caused by abnormally or excessively enhanced oxidative stress, are efficacious in the model of PD (19). From these reports, it can be hypothesized that telomere length shortening may be accelerated in PD patients. Telomere length in peripheral leukocytes can be an indicator of systemic PD-associated damages caused by oxidative stress and increased leukocyte turnover with chronic inflamma- tion, which accelerate age-related telomere length changes. 467 Journal of Gerontology: BIOLOGICAL SCIENCES Copyright 2008 by The Gerontological Society of America 2008, Vol. 63A, No. 5, 467–473 by guest on July 8, 2015 http://biomedgerontology.oxfordjournals.org/ Downloaded from