Novel Associations of Anxiety, Depression and Telomeres across Mid- and Late-Life

描述（由申请人提供）：焦虑和抑郁都与老年人的实质性功能和生活质量损害有关，并且与老年人过度代表的主要疾病（如心血管疾病和癌症）的发展有关。事实上，慢性精神疾病现在被假设为在高氧化应激条件下通过端粒缩短加速衰老的一种模式。有趣的是，最近的基础科学证据表明，高负荷的氧化应激可能会导致异常的情绪症状，如焦虑和恐惧。然而，这项工作的意义，更高的累积氧化应激和加速的生物衰老可能使个体易患晚年焦虑或抑郁的可能性，在人类中仍然相对未被探索。因此，以寿命为导向的方法来解决情绪和端粒长度提供了一个理想的策略，本项目旨在确定和表征端粒长度与恐惧焦虑和抑郁之间潜在的相互关联。通过利用现有数据，以及收集关于端粒长度和心理健康结果的新数据，来自一项长期的女性参与者的大型队列研究（护士健康研究），我们计划前瞻性地研究：1)10年内中年焦虑和抑郁与端粒长度变化的关系；2)中年端粒长度与晚年焦虑、抑郁的发展关系。此外，通过探索医疗条件的调解，如血管疾病和风险因素，我们可以阐明途径-解决是否有任何已确定的端粒-心理健康关联可以部分解释为医疗合并症。总之，本研究将对一种创新的临床转化模型进行假设检验，在该模型中，端粒缩短不仅可能是心理困扰的结果，而且可以在早期生命窗口期进行评估，以预测晚年的焦虑和抑郁。此外，研究目标将以巨大的成本和资源效率来实现。研究结果可以丰富对晚年焦虑和抑郁的生物学理解，为涉及端粒的新途径提供信息，以及未来解决这些途径的新治疗方法的可能性。

DESCRIPTION (provided by applicant): Anxiety and depression are both associated with substantial functional and quality of life impairment in older adults, and are related to development of major morbidities over- represented in aging, such as cardiovascular disease and cancer. Indeed, chronic mental disorders are now hypothesized to represent a model for accelerated aging via telomere shortening under conditions of high oxidative stress. Intriguingly, recent basic science evidence has demonstrated that high loading of oxidative stress may induce abnormal mood symptoms, such as anxiety and fear. However, implications of this work, the possibility that higher cumulative oxidative stress and accelerated biological aging may predispose individuals to later- life anxiety or depression - remain relatively unexplored in humans. Thus, a lifespan-oriented approach to addressing mood and telomere lengths provides an ideal strategy, and this project aims to identify and characterize potential reciprocal associations of phobic anxiety and depression with telomere length. By leveraging existing data, as well as collecting new data on telomere lengths and mental health outcomes, from a long-standing, large cohort study of female participants (the Nurses' Health Study), we plan to examine prospectively the relations of: 1) mid-life anxiety and depression to telomere length change over 10 years; 2) mid-life telomere length to development of later-life anxiety and depression. Further, by exploring mediation by medical conditions, such as vascular diseases and risk factors, we can elucidate pathways - addressing whether any identified telomere-mental health associations are explained, in part, by medical comorbidity. In summary, this study will conduct hypothesis testing of an innovative clinical translational model in which telomere shortening not only may be a consequence of psychological distress but also may be assessed at earlier life windows to predict later-life anxiety and depression. In addition, study aims will be achieved with enormous cost- and resource-efficiency. Findings could enrich biologic understanding of late-life anxiety and depression, informing new pathways involving telomeres, along with the possibility of novel future treatments addressing such pathways.