Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Department of Psychiatry, University Medical Center Utrecht Brain Center, University of Utrecht, Utrecht, the Netherlands.
Biol Psychiatry. 2023 Nov 1;94(9):694-705. doi: 10.1016/j.biopsych.2023.02.001. Epub 2023 Feb 9.
Individuals with psychiatric disorders are at increased risk of age-related diseases and early mortality. Recent studies demonstrate that this link between mental health and aging is reflected in epigenetic clocks, aging biomarkers based on DNA methylation. The reported relationships between epigenetic clocks and mental health are mostly correlational, and the mechanisms are poorly understood. Here, we review recent progress concerning the molecular and cellular processes underlying epigenetic clocks as well as novel technologies enabling further studies of the causes and consequences of epigenetic aging. We then review the current literature on how epigenetic clocks relate to specific aspects of mental health, such as stress, medications, substance use, health behaviors, and symptom clusters. We propose an integrated framework where mental health and epigenetic aging are each broken down into multiple distinct processes, which are then linked to each other, using stress and schizophrenia as examples. This framework incorporates the heterogeneity and complexity of both mental health conditions and aging, may help reconcile conflicting results, and provides a basis for further hypothesis-driven research in humans and model systems to investigate potentially causal mechanisms linking aging and mental health.
患有精神障碍的个体罹患与年龄相关的疾病和早逝的风险增加。最近的研究表明，心理健康和衰老之间的这种联系反映在基于 DNA 甲基化的衰老生物标志物——表观遗传钟上。报道的表观遗传钟与心理健康之间的关系大多是相关的，其机制尚不清楚。在这里，我们回顾了与表观遗传钟相关的分子和细胞过程的最新进展，以及能够进一步研究表观遗传衰老原因和后果的新技术。然后，我们回顾了目前关于表观遗传钟如何与心理健康的特定方面（如压力、药物、物质使用、健康行为和症状群）相关的文献。我们提出了一个综合框架，其中将心理健康和表观遗传衰老各自细分为多个不同的过程，然后使用压力和精神分裂症作为示例，将这些过程相互联系起来。该框架包含了心理健康状况和衰老的异质性和复杂性，可能有助于调和相互矛盾的结果，并为进一步在人类和模型系统中进行假设驱动的研究提供基础，以调查将衰老和心理健康联系起来的潜在因果机制。
