THE SENDEP STUDY: LINKING MOLECULAR SENESCENCE CHANGES TO DEPRESSION AND COGNITIVE IMPAIRMENT IN LATE LIFE

项目摘要 老年抑郁症是老年人常见的精神障碍， 从1%到5%不等。最近的证据表明，LLD与年龄相关的负面影响有关。 健康结果，如脑血管疾病，阿尔茨海默病的风险增加， 血管性痴呆和过早死亡。LLD的机制复杂， 涉及不同生物途径的失调。了解相互作用， 衰老和抑郁症的生物学变化可以提供对机制的深入了解， LLD会增加负面健康结果的风险。 本研究旨在评估衰老相关分泌物与 表型（SASP）指数与不同的衰老临床表型（即，认知障碍） 并且具有细胞衰老表型（即，白细胞端粒[LT]磨损）。最后， 我们将评估SASP变化的轨迹，以及它与认知功能的关系。 这些人的表现。 我们的假设是，LLD个体将显示出显着更高的SASP指数相比， 年龄和性别匹配的从未抑郁的对照组。SASP指数将显著 与LLD受试者中更大的认知障碍和端粒磨损相关。我们进一步 假设增加或持续较高的SASP指数轨迹将导致更快 研究参与者在两年的随访中认知能力下降。 据我们所知，这将是第一项研究，以检查之间的联系循环 分子衰老标志物（SASP），细胞衰老标志物（LT磨耗），和 LLD的神经认知和临床特征。根据这项研究的结果，我们还将 能够为制定干预措施确定新的目标， 治疗老年抑郁症，但也旨在预防不良后果 与这种情况有关。

Project Summary Late-life depression (LLD) is a common mental disorder in the elderly, with prevalence rates ranging from 1 to 5%. Recent evidence suggests that LLD is linked to age-related negative health outcomes, such as cerebrovascular disease, increased risk of Alzheimer's disease, vascular dementia, and of premature mortality. The mechanisms of LLD are complex and involve the dysregulation of different biological pathways. Understanding the interplay between the biological changes in aging and depression can provide insight into the mechanisms by which LLD increases the risk of negative health outcomes. This study proposes to evaluate the association of Senescence-Associated Secretory Phenotype (SASP) Index with different clinical phenotypes of aging (i.e., cognitive impairment) and with cellular senescence phenotype (i.e., leukocyte telomere [LT] attrition) in LLD. Finally, we will evaluate the trajectory of changes in SASP, and its relationship with cognitive performance in these individuals. Our hypotheses are that LLD individuals will show a significantly higher SASP index compared to age- and gender-matched never-depressed control subjects. SASP index will be significantly associated with greater cognitive impairment and telomere attrition in LLD subjects. We further hypothesize that an increasing or persistently higher SASP index trajectory will lead to faster cognitive decline among study participants over two years of follow-up. To our knowledge, this will be the first study to examine the association between circulating molecular senescence markers (SASP), a cellular senescence marker (LT attrition), and neurocognitive and clinical characteristics in LLD. Based on the results of this study, we will also be able to identify novel targets for the development of interventions aiming not only the treatment of depression in the elderly but also aiming the prevention of the negative outcomes related to this condition.