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结节病患者端粒亚端粒甲基化的衰老相关改变。

Aging-related alterations of subtelomeric methylation in sarcoidosis patients.

作者信息

Maeda Toyoki, Guan Jing Zhi, Higuchi Yoshihiro, Oyama Jun-ichi, Makino Naoki

机构信息

Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Tsurumihara, Beppu, Oita, Japan.

出版信息

J Gerontol A Biol Sci Med Sci. 2009 Jul;64(7):752-60. doi: 10.1093/gerona/glp049. Epub 2009 May 4.

Abstract

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.

摘要

体细胞中的端粒会随着衰老而变短,并且在病理生理条件下这种缩短会加速。端粒缩短会受到亚端粒DNA甲基化的影响。我们比较了健康对照组和结节病患者外周血白细胞中的端粒长度和亚端粒甲基化状态。与健康对照组相比,结节病患者的端粒更短,端粒缩短的损耗更快。健康对照组和结节病患者均显示,随着衰老,长端粒(>9.4 kb)减少,短端粒(<4.4 kb)增加,同时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亚端粒低甲基化有关。此外,结节病患者比亚端粒甲基化改变(在60多岁或更晚)的对照组更早出现这种情况。这种亚端粒低甲基化的改变可能与结节病中端粒缩短加速相对应。这也意味着亚端粒低甲基化也可能受到某些疾病状况的影响。

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