Hozakowska-Roszkowska Dominika Marzena, Mengel-From Jonas, Hristozova Teodora K, Pedersen Jacob Krabbe, Jeune Bernard, Andersen-Ranberg Karen, Hjelmborg Jacob V B, Christensen Kaare, Röttger Richard, Nygaard Marianne
Department of Mathematics and Computer Science, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
Mech Ageing Dev. 2024 Dec;222:111979. doi: 10.1016/j.mad.2024.111979. Epub 2024 Sep 16.
Mosaic loss of the Y chromosome (mLOY) is a common somatic mutation in the blood of elderly men and several studies have found mLOY in blood cells to be associated with an increased risk of various diseases and mortality. However, most of these studies have focused on middle-aged and older adults, meaning that mLOY in extremely old individuals like centenarians is understudied. To explore mLOY across a wider age range compared to earlier studies and to specifically focus on centenarians, mLOY was estimated in 917 Danish men aged 56-100 years. We found that the percentage of men with LOY increased with age until age 85, after which it plateaued at around 40 %. Consistently, a longitudinal comparison of mLOY revealed that mLOY predominantly increased with age, although inter-individual variation was seen. Using a twin sub-sample, the broad-sense heritability of mLOY was estimated at 72 %, indicating a substantial genetic influence. Supporting previous findings, mLOY was found to associate with increased mortality across all study participants and in men younger than 80 years. In centenarians, however, a higher level of mLOY associated with better survival, most likely due to selection, although confirmation of our findings in larger studies is needed.
Y染色体嵌合缺失（mLOY）是老年男性血液中常见的体细胞突变，多项研究发现血细胞中的mLOY与多种疾病风险增加及死亡率上升有关。然而，这些研究大多集中在中老年人，这意味着像百岁老人这样的极长寿个体中的mLOY研究不足。为了比早期研究更广泛地探索不同年龄段的mLOY，并特别关注百岁老人，我们对917名年龄在56至100岁的丹麦男性进行了mLOY评估。我们发现，LOY男性的比例随年龄增长而增加，直至85岁，此后稳定在40%左右。同样，mLOY的纵向比较显示，尽管存在个体差异，但mLOY主要随年龄增长而增加。利用双胞胎子样本，mLOY的广义遗传率估计为72%，表明存在重大遗传影响。与之前的研究结果一致，在所有研究参与者以及80岁以下男性中，mLOY与死亡率增加有关。然而，在百岁老人中，较高水平的mLOY与更好的生存率相关，这很可能是由于选择因素，不过需要在更大规模的研究中证实我们的发现。
