Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, 1941 East Rd, Houston, TX, 77054, USA; Center of Excellence in Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, 1941 East Rd, Houston, TX, 77054, USA.
Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, 1941 East Rd, Houston, TX, 77054, USA.
J Psychiatr Res. 2024 Dec;180:291-300. doi: 10.1016/j.jpsychires.2024.10.026. Epub 2024 Oct 23.
Bipolar disorder (BD) has been linked to accelerated aging processes, with many studies suggesting that drugs used to treat BD may modulate pathways related to aging. This systematic review aimed to determine whether FDA-approved pharmacotherapies for BD have reported effects on aging biomarkers across clinical and preclinical studies. We conducted searches in PubMed and PsychINFO and followed PRISMA guidelines. Out of 6400 records identified, 19 studies met the inclusion criteria. Most preclinical studies tested the effects of BD drugs, especially lithium, on lifespan and telomere biology in cell and animal models. Clinical studies predominantly focused on lithium, evaluating aging markers like telomere length, telomerase, mitochondrial DNA copy number, and epigenetic age acceleration in individuals with BD. Findings indicate that chronic lithium treatment is associated with modulatory effects on aging biomarkers, particularly increased telomere length and telomerase activity. Conversely, some negative results were also reported. Limited evidence suggests potential aging-modulating properties of other mood stabilizers like valproic acid and lamotrigine, evidencing that further investigation is required. Despite variability across studies, the overall findings support the notion that pharmacotherapies used in BD present many effects of aging biomarkers. However, the field is still developing, with a clear emphasis on lithium and a lack of standardized methods to evaluate aging biomarkers in clinical samples. Further research exploring the anti-accelerated aging effects of BD drugs beyond lithium, their mechanisms of action, and potential synergistic effects is warranted.
双相障碍 (BD) 与加速衰老过程有关，许多研究表明，用于治疗 BD 的药物可能调节与衰老相关的途径。本系统评价旨在确定 FDA 批准的 BD 治疗药物在临床前和临床研究中是否报告了对衰老生物标志物的影响。我们在 PubMed 和 PsychINFO 中进行了检索，并遵循 PRISMA 指南。在确定的 6400 条记录中，有 19 项研究符合纳入标准。大多数临床前研究测试了 BD 药物的影响，特别是锂，对细胞和动物模型中的寿命和端粒生物学的影响。临床研究主要集中在锂上，评估 BD 个体的衰老标志物，如端粒长度、端粒酶、线粒体 DNA 拷贝数和表观遗传年龄加速。研究结果表明，慢性锂治疗与衰老生物标志物的调节作用有关，特别是端粒长度和端粒酶活性增加。相反，也有一些负面结果的报道。有限的证据表明其他心境稳定剂，如丙戊酸和拉莫三嗪，可能具有潜在的衰老调节特性，这表明需要进一步研究。尽管研究之间存在差异，但总体研究结果支持这样一种观点，即 BD 中使用的药物对衰老生物标志物有多种影响。然而，该领域仍在发展中，重点是锂，缺乏评估临床样本中衰老生物标志物的标准化方法。需要进一步研究探索除锂以外的 BD 药物的抗加速衰老作用、它们的作用机制以及潜在的协同作用。
