Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth), 1941 East Rd, 77054, Houston, TX, USA.
Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
Transl Psychiatry. 2017 Dec 11;7(12):1283. doi: 10.1038/s41398-017-0048-8.
Bipolar disorder (BD) has been previously associated with accelerated aging; yet, the mechanisms underlying this association are largely unknown. The epigenetic clock has been increasingly recognized as a valuable aging marker, although its association with other biological clocks in BD patients and high-risk subjects, such as telomere length and mitochondrial DNA (mtDNA) copy number, has never been investigated. We included 22 patients with BD I, 16 siblings of BD patients, and 20 healthy controls in this analysis. DNA was isolated from peripheral blood and interrogated for genome-wide DNA methylation, mtDNA copy number, and telomere length. DNA methylation age (DNAm age) and accelerated aging were calculated using the Horvath age estimation algorithm in blood and in postmortem brain from BD patients and nonpsychiatric controls using publicly available data. Older BD patients presented significantly accelerated epigenetic aging compared to controls, whereas no difference was detected among the younger subjects. Patients showed higher levels of mtDNA copy number, while no difference was found between controls and siblings. mtDNA significantly correlated with epigenetic age acceleration among older subjects, as well and with global functioning in our sample. Telomere length did not show significant differences between groups, nor did it correlate with epigenetic aging or mtDNA copy number. These results suggest that BD may involve an accelerated epigenetic aging, which might represent a novel target for treating BD and subjects at risk. In particular, our results suggest a complex interplay between biological clocks to determine the accelerated aging and its consequences in BD.
双相情感障碍（BD）以前与加速衰老有关；然而，这种关联的机制在很大程度上尚不清楚。表观遗传钟越来越被认为是一种有价值的衰老标志物，尽管它与 BD 患者和高风险人群（如端粒长度和线粒体 DNA（mtDNA）拷贝数）中的其他生物钟的关联从未被研究过。我们在这项分析中纳入了 22 名 BD I 患者、16 名 BD 患者的兄弟姐妹和 20 名健康对照者。从外周血中分离 DNA，并检测全基因组 DNA 甲基化、mtDNA 拷贝数和端粒长度。使用 Horvath 年龄估算算法在血液中计算 DNA 甲基化年龄（DNAm 年龄）和加速衰老，并使用 BD 患者和非精神科对照者的公开可用数据在死后大脑中计算 DNAm 年龄和加速衰老。与对照组相比，年龄较大的 BD 患者表现出明显加速的表观遗传衰老，而年轻患者则没有差异。患者的 mtDNA 拷贝数较高，而对照组和兄弟姐妹之间没有差异。mtDNA 与老年患者的表观遗传加速衰老以及我们样本中的整体功能显著相关。各组之间端粒长度没有显著差异，也与表观遗传衰老或 mtDNA 拷贝数无关。这些结果表明，BD 可能涉及加速的表观遗传衰老，这可能是治疗 BD 和高危人群的新靶点。特别是，我们的结果表明，生物钟之间存在复杂的相互作用，以确定 BD 中的加速衰老及其后果。
