Effect of Vitamin E Administration on the Elevated Oxygen Stress and the Telomeric and Subtelomeric Status in Alzheimer’s Disease

Abstract

Background: Oxidative stress (OS) may be involved in the neurodegenerative process in Alzheimer’s disease (AD). Telomeres, the repeated sequences that cap chromosome ends, undergo shortening with each cell division, are sensitive to OS, and serve as markers of a cell’s replicative history. Telomere length shortening has been reported to relate to OS with aging process and aging-associated diseases, but the telomeric changes were not always identical, especially in change of telomere length distribution and subtelomeric methylation. The involvement of an OS-associated telomere change in the pathogenesis of AD has been discussed for decades, and the telomere length and telomerase activity were analyzed. However, other telomeric factors, such as the telomere distribution and subtelomeric methylation status, have not yet been analyzed. Objective: The subtelomeric methylation status as well as the telomere length were studied in AD with an antioxidant vitamin in terms of OS. Methods: We measured urinary 8-iso-PGF2α, a lipid-peroxidation product as an OS marker, and methylated and non-methylated telomere lengths in the peripheral blood mononuclear cells by Southern blotting in AD patients before and after vitamin E treatment. Results: The level of urinary 8-iso-PGF2α was found to have increased in AD. Middle-ranged telomeres (4.4–9.4 kb) increased and the shortest telomeres (<4.4 kb) decreased in AD patients. Telomeres were more methylated in both long telomeres and in short telomeres in AD compared with the control. The oral administration of the antioxidant vitamin E in 400 mg/day for 6 months in AD patients partly reversed AD-associated alterations in OS marker levels. Conclusions: AD patients showed an elevated OS marker level, and vitamin E lowered the OS level. In comparison with controls, AD patients showed shorter telomere lengths. Cells with short and long telomeres bore relatively hypermethylated subtelomeres in AD patients. Aging-associated accumulation of cells bearing short telomeres was not observed in AD. These results imply that long telomeres with hypomethylation tend to shorten faster, and cells bearing short telomeres with hypomethylation tend to more easily enter into a senescent state under elevated OS stress in AD. However, no significant effect on the altered telomeric profiles in AD patients could be detected after a 6-month administration of vitamin E.

Association Between Leukocyte Telomere Length and Plasma Homocysteine in a Singapore Chinese Population

“…39 In addition, a study in a Chinese population with similar age range of participants as our study reported that the LTL was generally less than 12,000 bp. 40 The association between HCY and telomeres was first explored by Bekaert et al in 2007 as part of a study in a Belgian cohort aimed at investigating the link between CVD risk markers and LTL. 15 However, an association between LTL and CVD risk markers, including cholesterol, TGs, blood pressure, and plasma HCY, was not found.…”

“…Thus, the remaining 90 samples were included in this study because TL < 2000 bp is normally found in individuals above 80 years, 39 and this exclusion criteria was also based on the range reported in Chinese populations (generally longest < 12,000 bp). 40 …”

Telomere Length and Its Relation to Human Health

“…It is relevant that both ascorbic acid (vitamin C) and tocopherol (vitamin E) are recognized antioxidants [116][117][118][119] that can prevent ROS generation, therefore increasing oxidative stress. For patients with Alzheimer's disease, elevated oxidative stress levels were found, besides shorter telomeres [120]. When vitamin E was administered to these patients, although there was no significant difference in telomere length after 6 months, levels of oxidative stress were lower [120].…”

“…For patients with Alzheimer's disease, elevated oxidative stress levels were found, besides shorter telomeres [120]. When vitamin E was administered to these patients, although there was no significant difference in telomere length after 6 months, levels of oxidative stress were lower [120].…”

Increased Telomere Length and Improvements in Dysautonomia, Quality of Life, and Neck and Back Pain Following Correction of Sagittal Cervical Alignment Using Chiropractic BioPhysics® Technique: a Case Study

“…Additionally, TL is associated with lifestyle choices such as diet, tobacco and alcohol use [12], physical activity, and sleep [3]. Fewer studies have focused on the dynamic change and regulation of TL by implementing exercise programs [13,14], vitamin supplements [15], diet [16], meditation [17], and genetic engineering [18]. Interest in telomere lengthening or length maintenance is due to the notion that this will serve to slow down or cease a person's biological clock providing youthfulness and health longevity [10].…”