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Aging and Disease (1)
Experimental & Clinical Cardiology (1)
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences (1)
Maeda, Toyoki (3)
Makino, Naoki (3)
Guan, Jing Zhi (1)
Guan, Jing-Zhi (1)
Guan, Wei-Ping (1)
Higuchi, Yoshihiro (1)
Mimori, Kosi (1)
Oyama, Jun-ichi (1)
Sasaki, Makoto (1)
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The Subtelomere of Short Telomeres is Hypermethylated in Alzheimer’s Disease
Aging and Disease
Telomere shortening has been reported to be related to oxidative stress (OS) associated with the aging process and aging-associated diseases, including Alzheimer’s disease (AD). We measured the methylated and non-methylated telomere lengths in the peripheral blood mononuclear cells of 34 AD patients and 49 healthy controls by a Southern blotting analysis, using methylation-sensitive and - insensitive restriction enzyme isoschizomers, MspI and HpaII. AD patients bore normal mean telomere lengths and had an unchanged distribution of the telomere length in peripheral leukocytes. However, the subtelomeres in the shortest telomeres were relatively more methylated in AD patients of both genders, compared with age-matched controls. We observed that the pathogenesis of AD was associated with the epigenetic condition of the subtelomere, but not on the overall telomere length and distribution. The relative elevation of subtelomeric methylation of short telomeres in peripheral blood leukocytes may be a characteristic of AD. This implies that leukocytes containing short telomeres with less methylated subtelomeres tend to be removed faster from the peripheral blood in AD patients.
Alzheimer’s disease; Telomere; Subtelomere; DNA methylation
Telomere biology in cardiovascular disease – role of insulin sensitivity in diabetic hearts
Experimental & Clinical Cardiology
The present study examined telomere biology in the context of insulin sensitivity in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetic animal model. To improve insulin sensitivity, pioglitazone (PG; 10 mg/kg/day) was administered to OLETF rats between 20 weeks and 40 weeks of age, and the effects of the treatment were compared with those in untreated OLETF rats or control Long-Evans Tokushima Otsuka rats. The homeostasis model assessment of insulin resistance index significantly increased in OLETF rats, but decreased in PG-treated OLETF rats. Telomere lengths were not shortened in heart tissues of OLETF rats; however, telomerase activity was decreased in heart tissues of OLETF rats. Messenger RNA expression for both telomerase reverse transcriptase and telomere repeat binding factor 2 was downregulated in the hearts of OLETF rats. Protein expression of phosphorylated Akt, insulin-like growth factor and endothelial nitric oxide synthase were all reduced in OLETF rats. The changes observed in OLETF rats were inhibited by PG treatment. Myocardial fibrosis was less extensive and diastolic dysfunction improved in PG-treated OLETF rats versus untreated OLETF rats. These findings suggest that improving insulin sensitivity via the activation of peroxisome proliferator-activated receptor-gamma may exert regulatory effects on cardiac telomere biology, and may have desirable morphological and functional effects on the diabetic heart.
Diabetes; Pioglitazone; PPAR-γ; Remodelling; Telomere
Age-Related Changes in Subtelomeric Methylation in the Normal Japanese Population
Guan, Jing Zhi
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
The telomeres of somatic cells become shorter with individual aging. However, no significant change in subtelomeric methylation of somatic cells with aging has yet been reported.
Telomere lengths of the peripheral blood cells of 148 normal Japanese were analyzed by Southern blotting using methylation-sensitive and -insensitive isoschizomers.
With aging, long telomeres decrease and short telomeres increase, and the contents of the telomeres with methylated subtelomere increase in long telomeres, thus leading us to postulate that telomeres with less methylated subtelomeres tend to become shortened faster.
A telomere length distribution analysis with methylation-sensitive and -insensitive isoschizomer seems to be a useful tool to assess the subtelomeric methylation status of the somatic cell population. The subtelomeric methylation of peripheral blood cells is also indicated to be an indicator for aging-associated genomic changes.
Telomere; Aging; DNA methylation; Japanese
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