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

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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.