Translational Psychiatry Program, Louis A. Faillace, MD, Department of Psychiatry & Behavioral Sciences, The University of Texas Health Science Center at Houston, 1941 East Rd, 77054, Houston, TX, USA; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, 7000 Fannin St, 77030, Houston, TX, USA; Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA.
Translational Psychiatry Program, Louis A. Faillace, MD, Department of Psychiatry & Behavioral Sciences, The University of Texas Health Science Center at Houston, 1941 East Rd, 77054, Houston, TX, USA.
J Psychiatr Res. 2020 Sep;128:38-42. doi: 10.1016/j.jpsychires.2020.05.022. Epub 2020 May 26.
Bipolar disorder (BD) has been previously associated with accelerated aging, and recent investigations have started to explore the potential anti-aging effects of BD treatments. Lithium, the most commonly used mood stabilizer, has been suggested to impact telomere length in specific populations, although its effects on other aging biomarkers, such as epigenetic aging, have never been investigated. We assessed the in vitro effects of lithium on telomere length and epigenetic aging in lymphoblastoid cell lines (LCLs) from 14 patients with BD and 14 controls, all matched for age, sex, and ethnicity. Our results showed that telomere length significantly correlated with chronological age in LCLs in both groups and that BD patients have shorter telomere lengths compared to controls at baseline (vehicle treatment), confirming previous in vivo findings. Moreover, lithium treatment significantly increased telomere length in LCLs from patients, but not in controls. On the other hand, epigenetic age did not correlate with chronological age and was not shown to differ between patients and controls. In addition, lithium did not induce any changes in epigenetic age in cells from either patients or controls. Overall, our results support previous reports of an anti-aging effect of lithium based on its modulation of telomere length and suggest a different lithium effect in cells from patients and controls. Finally, we also discuss the limitations of using transformed LCLs for the study of DNA methylation mechanisms.
双相情感障碍 (BD) 先前与加速衰老有关,最近的研究开始探索 BD 治疗的潜在抗衰老作用。锂,最常用的情绪稳定剂,被认为会影响特定人群的端粒长度,尽管它对其他衰老生物标志物(如表观遗传衰老)的影响从未被研究过。我们评估了锂对来自 14 名 BD 患者和 14 名对照组的淋巴母细胞系 (LCL) 中端粒长度和表观遗传衰老的体外影响,所有患者和对照组均按年龄、性别和种族匹配。我们的结果表明,在两组的 LCL 中,端粒长度与年龄呈显著相关性,并且与对照组相比,BD 患者的端粒长度在基线(载体治疗)时更短,证实了先前的体内发现。此外,锂处理可显著增加患者的 LCL 中端粒长度,但不能增加对照组的 LCL 中端粒长度。另一方面,表观遗传年龄与年龄无关,且在患者和对照组之间没有差异。此外,锂在患者和对照组的细胞中均未引起表观遗传年龄的任何变化。总体而言,我们的结果支持基于锂对端粒长度的调节的锂具有抗衰老作用的先前报告,并表明锂在患者和对照组的细胞中有不同的作用。最后,我们还讨论了使用转化的 LCL 研究 DNA 甲基化机制的局限性。