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

项目摘要 老年抑郁症(LLD)是一种常见的老年人精神障碍，患病率较高 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 健康后果，如脑血管疾病，阿尔茨海默病风险增加， 血管性痴呆症和过早死亡。LLD的机制很复杂，而且 涉及不同生物途径的失调。了解两者之间的相互影响 衰老和抑郁的生物学变化可以通过以下方式提供对机制的洞察 这种LLD增加了负面健康结果的风险。 这项研究建议评估衰老相关的分泌物的关联性 衰老(即认知障碍)不同临床表型的表型(SASP)指数 LLD伴有细胞衰老表型(即白细胞端粒[LT]磨损)。最后， 我们将评估SASP的变化轨迹，以及它与认知的关系 在这些人身上的表现。 我们的假设是，与LLD个体相比，LLD个体的SASP指数显著更高 年龄和性别匹配的从未抑郁的对照组受试者。SASP指数将大幅上升 与LLD受试者更大的认知障碍和端粒磨损有关。我们进一步 假设SASP指数轨迹不断增加或持续较高将导致更快 研究参与者在两年多的跟踪调查中认知能力下降。 据我们所知，这将是第一次研究循环与 分子衰老标志物(SASP)，一种细胞衰老标志物(LT磨损)，以及 LLD的神经认知和临床特点。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，目标不仅是 治疗老年抑郁症的同时也旨在预防其负面后果 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.