Shindo Ryota, Tanifuji Takaki, Okazaki Satoshi, Otsuka Ikuo, Shirai Toshiyuki, Mouri Kentaro, Horai Tadasu, Hishimoto Akitoyo
Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.
NPJ Aging. 2023 Sep 6;9(1):19. doi: 10.1038/s41514-023-00117-1.
Major depressive disorder (MDD) is known to cause significant disability. Genome-wide DNA methylation (DNAm) profiles can be used to estimate biological aging and as epigenetic clocks. However, information on epigenetic clocks reported in MDD patients is inconsistent. Since antidepressants are likely confounders, we evaluated biological aging using various DNAm-based predictors in patients with MDD who had never received depression medication. A publicly available dataset consisting of whole blood samples from untreated MDD patients (n = 40) and controls (n = 40) was used. We analyzed five epigenetic clocks (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge), DNAm-based telomere length (DNAmTL), and DNAm-based age-related plasma proteins (GrimAge components), as well as DNAm-based white blood cell composition. The results indicate that patients with untreated MDD were significantly associated with epigenetic aging acceleration in HannumAge and GrimAge. Furthermore, a decrease in natural killer cells, based on DNAm, was observed in patients with untreated MDD.
重度抑郁症（MDD）会导致严重的残疾。全基因组DNA甲基化（DNAm）图谱可用于估计生物衰老，并作为表观遗传时钟。然而，关于MDD患者表观遗传时钟的报道信息并不一致。由于抗抑郁药可能是混杂因素，我们在从未接受过抑郁症药物治疗的MDD患者中，使用各种基于DNAm的预测指标评估了生物衰老情况。我们使用了一个公开可用的数据集，该数据集由未接受治疗的MDD患者（n = 40）和对照组（n = 40）的全血样本组成。我们分析了五个表观遗传时钟（HorvathAge、HannumAge、SkinBloodAge、PhenoAge和GrimAge）、基于DNAm的端粒长度（DNAmTL）、基于DNAm的与年龄相关的血浆蛋白（GrimAge成分）以及基于DNAm的白细胞组成。结果表明，未接受治疗的MDD患者与HannumAge和GrimAge中的表观遗传衰老加速显著相关。此外，在未接受治疗的MDD患者中，基于DNAm观察到自然杀伤细胞减少。
