Pohl Eva, Muschal Sina, Kliesch Sabine, Zitzmann Michael, Rohayem Julia, Gromoll Jörg, Laurentino Sandra
1Institute for Human Genetics, University of Münster, 48149 Münster, Germany.
2Department of Clinical and Surgical Andrology, Centre of Reproductive Medicine and Andrology, University of Münster, 48149 Münster, Germany.
Aging Dis. 2020 May 9;11(3):470-476. doi: 10.14336/AD.2019.0801. eCollection 2020 May.
Molecular aging markers provide the opportunity for biological age determination in humans and to study factors, such as genetic determinants, affecting the ageing process. In males with Klinefelter syndrome (KS, non-mosaic karyotype 47, XXY), which is the most common sex chromosome aneuploidy, age-related morbidity and mortality are increased, and a significantly reduced life span has been observed. The aim of this study was to investigate whether Klinefelter patients exhibit molecular signs of premature ageing. We studied, specifically, age-associated DNA methylation patterns (by pyrosequencing) and relative telomere length (TL; by quantitative polymerase chain reaction) in blood in a cohort of Klinefelter patients (n=178 and 266 for DNA methylation and TL, respectively) aged 18-71 years and compared them to the data of age-matched healthy male (n = 184 and 196 for DNA methylation and TL, respectively) and female controls (n = 50). Age-associated DNA methylation patterns were not indicative of accelerated ageing in Klinefelter men. Significantly longer telomeres were found in the young Klinefelter subjects aged 18-24 years (mean=1.51 vs. 1.09 and 1.26 in female and male controls, respectively). However, telomere length in subsequent age groups showed no difference to controls. Gonosomal aneuploidy in Klinefelter syndrome is associated with higher baseline TL at adolescent age, but comparable TL with progressive age in other age groups.
分子衰老标志物为确定人类生物学年龄以及研究影响衰老过程的因素（如基因决定因素）提供了机会。在患有克兰费尔特综合征（KS，非嵌合核型47，XXY）的男性中，这是最常见的性染色体非整倍体，与年龄相关的发病率和死亡率增加，并且观察到寿命显著缩短。本研究的目的是调查克兰费尔特综合征患者是否表现出早衰的分子迹象。我们具体研究了18至71岁的克兰费尔特综合征患者队列（分别有178例和266例用于DNA甲基化和端粒长度研究）血液中与年龄相关的DNA甲基化模式（通过焦磷酸测序）和相对端粒长度（TL；通过定量聚合酶链反应），并将其与年龄匹配的健康男性（分别有184例和196例用于DNA甲基化和TL研究）和女性对照（50例）的数据进行比较。与年龄相关的DNA甲基化模式并未表明克兰费尔特综合征男性存在加速衰老。在18至24岁的年轻克兰费尔特综合征患者中发现端粒显著更长（女性和男性对照的平均值分别为1.09和1.26，而该组平均值为1.51）。然而，随后年龄组的端粒长度与对照组无差异。克兰费尔特综合征中的性染色体非整倍体与青春期较高的基线端粒长度相关，但在其他年龄组中随着年龄增长端粒长度与对照组相当。
