Rivero-Segura Nadia Alejandra, Cuartas Julian Daniel Rodriguez, Garcia-delaTorre Paola, Sanchez-Garcia Sergio, Ramirez-Aldana Ricardo, Gomez-Verjan Juan Carlos
Dirección de Investigación, Instituto Nacional de Geriatría (INGER), 10200, Mexico City, Mexico.
Unidad de Investigación Epidemiológica y en Servicios de Salud, Área de Envejecimiento, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, 06720, Mexico City, Mexico.
Geroscience. 2025 Mar 18. doi: 10.1007/s11357-025-01608-7.
Insomnia is a common sleep disorder characterized mainly by poor sleep quality and insufficient sleep duration. It affects a significant proportion of the global population and is correlated with physical and mental consequences such as cognitive decline, anxiety, chronic fatigue, poor concentration, and memory impairment. Interestingly, it is also linked to ageing and age-related diseases (cardiovascular, metabolic, and neurodegenerative). On the other hand, as we age, DNA methylation patterns undergo significant changes. These have been used to develop the so-called epigenetic clocks that estimate the biological age linked to the environment and the risk of diseases. Few studies have evaluated the association between insomnia and epigenetic clocks, providing insight into the role of insomnia in ageing acceleration. Therefore, in the present study, we carried out an epigenetic analysis by using Illumina EPICv.2 array on 63 older adults (> 60 years old, n = 33 with insomnia vs. n = 30 control) to evaluate the relation between insomnia and epigenetic ages (HorvathAGE, HannumAGE, PhenoAGE, SkinBloodClock, GrimAGE, DunedinPACE, DNAmTL). As a result, we found an increased acceleration and correlation between GrimAGE and SkinBloodClock and a significant reduction in the DNAmTL in individuals with insomnia. An EWAS analysis showed a global pattern of hypomethylation and an enrichment of several proteostasis and oxidative pathways. In conclusion, our results suggest that insomnia increases GrimAGE and SkinBloodClock acceleration and may be participating in telomere shortening. Additionally, changes in DNA methylation patterns induced by insomnia impact proteostasis and oxidative stress.
失眠是一种常见的睡眠障碍，主要特征为睡眠质量差和睡眠时间不足。它影响着全球相当大比例的人口，并与认知能力下降、焦虑、慢性疲劳、注意力不集中和记忆力减退等身心后果相关。有趣的是，它还与衰老及与年龄相关的疾病（心血管疾病、代谢疾病和神经退行性疾病）有关。另一方面，随着年龄的增长，DNA甲基化模式会发生显著变化。这些变化已被用于开发所谓的表观遗传时钟，以估计与环境相关的生物年龄和疾病风险。很少有研究评估失眠与表观遗传时钟之间的关联，这为深入了解失眠在加速衰老中的作用提供了线索。因此，在本研究中，我们对63名老年人（>60岁，n = 33名失眠患者与n = 30名对照者）使用Illumina EPICv.2芯片进行了表观遗传分析，以评估失眠与表观遗传年龄（HorvathAGE、HannumAGE、PhenoAGE、SkinBloodClock、GrimAGE、DunedinPACE、DNAmTL）之间的关系。结果，我们发现失眠个体的GrimAGE和SkinBloodClock加速增加且存在相关性，DNAmTL显著降低。一项全基因组关联研究分析显示出整体低甲基化模式以及几种蛋白质稳态和氧化途径的富集。总之，我们的结果表明，失眠会增加GrimAGE和SkinBloodClock的加速，并可能参与端粒缩短。此外，失眠引起的DNA甲基化模式变化会影响蛋白质稳态和氧化应激。
