Aging-Related Alterations of Subtelomeric Methylation in Sarcoidosis Patients

Aging-Related Alterations of Subtelomeric Methylation in Sarcoidosis Patients
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DOI:
10.1093/gerona/glp049
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发表时间:
2009-07-01
影响因子:
5.1
通讯作者:
Makino, Naoki
Makino, Naoki
中科院分区:
医学1区
文献类型:
--
作者:
Maeda, Toyoki;Guan, Jing Zhi;Makino, Naoki

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体细胞中的端粒随着衰老而变短,并且病理生理条件会加速缩短。端粒缩短可能受到亚端粒 DNA 甲基化的影响。比较健康对照和结节病患者外周白细胞的端粒长度和亚端粒甲基化状态。与健康对照相比,结节病患者的端粒较短,而且端粒缩短的磨损速度更快。健康对照和结节病患者均显示,随着年龄的增长,长端粒(> 9.4 kb)减少,短端粒(< 4.4 kb)增加,伴随亚端粒高甲基化的长端粒和亚端粒低甲基化的短端粒相对增加。这表明与衰老相关的端粒缩短与周围的亚端粒低甲基化有关。此外,结节病患者比对照组(60 多岁或更晚)更早表现出亚端粒甲基化的改变。这种改变的亚端粒低甲基化可能与结节病中端粒加速缩短相对应。这也意味着亚端粒低甲基化也会受到某些疾病的影响。
Telomeres in somatic cells become shorter with aging, and the shortening is accelerated by pathophysiological conditions. Telomere shortening can be influenced by subtelomeric DNA methylation. The telomere length and subtelomeric methylation status in peripheral leukocytes were compared in healthy controls and sarcoidosis patients. The sarcoidosis patients revealed shorter telomeres and a faster attrition of telomere shortening in comparison with healthy controls. Both healthy controls and sarcoidosis patients showed that long telomeres (> 9.4 kb) decrease and short telomeres (< 4.4 kb) increase with aging, accompanying relative increases of long telomeres with subtelomeric hypermethylation and short telomeres with subtelomeric hypomethylation. This suggested that the aging-related telomere shortening is associated with the surrounding subtelomeric hypomethylation. Furthermore, sarcoidosis patients showed this alteration of the subtelomeric methylation earlier than controls (in their 60s or later). This altered subtelomeric hypomethylation may correspond to the accelerated telomere shortening in sarcoidosis. This also means that the subtelomeric hypomethylation can be also influenced by certain disease conditions.