The Long Life Family Study

摘要 长寿家庭研究(LLFS)是一组异常健康的个体，他们表现出更长的健康跨度 痴呆症、心脏病和中风的发病明显延迟。LLFS的参与者还展示了 健康衰老表型(HAP)的丰富，包括几个生物学结构域，如例外 记忆力、握力、肺功能、血压和/或新陈代谢。由于LLFS招募了家庭 显示出长寿的家族聚集性，即使是较年轻的参与者也可能有保护因素使他们 增加了自己获得异常长寿的可能性。然而，接触SARS-CoV-2 病毒很可能是LLFS未来健康的重要风险/保护因素决定因素 参与者。特别是，有证据表明，可能会长期增加心血管疾病的风险，如心肌炎。 以及受影响幸存者的中风或认知障碍。这项建议旨在增强现有的优势。 LLFS，包括纵向详细的表型和系列多组学分析，以确定各种 通过对暴露于SARS-CoV-2的病毒进行抗体测试来评估健康结果，并帮助对LLFS进行分类 参与者被诊断为新冠肺炎感染的有症状个人，无症状的冠状病毒携带者- 19感染者，以及未感染新冠肺炎者或未患该病者。截至日期，SARS-CoV-2 抗体研究几乎完全集中在基于血液的抗体反应和粘膜免疫。 鼻咽部和口咽部是SARS-CoV-2感染的主要部位，目前仍知之甚少。 因此，这项研究将检测唾液中的SARS-CoV-2抗体，以将参与者的风险降至最低，并提供 估计这一人群的粘膜免疫力。具体地说，这一行政副刊将采取措施 唾液中SARS-CoV-2不同亚型抗体(Ig G和Ig A)的检测(目标1)，并测量定量水平 这两种抗体的亚型(目标2)。我们将利用自己收集的唾液样本来实现这两个目标 使用内部SARS-CoV-2酶联免疫吸附试验和商业化的FDA-EUA批准的试验进行分析 (罗氏公司)这将能够区分由自然感染产生的SARS-CoV-2抗体 或者接种疫苗。我们将使用基于家庭的多变量广义线性模型来检验SARS与 冠状病毒-2抗体(同种类型和定量水平)与衰老轨迹以及随后的跟踪- 增加有关发病率和死亡率的数据。这种方法将使我们能够估计 在控制了其他已知危险因素和措施后，对感兴趣的结果的SARS-CoV-2抗体 (包括各种经济学)。因此，确定接触过SARS-CoV-2感染的LLFS参与者将 提供一个机会来评估SARS-CoV-2感染对几个HAP轨迹的影响 LLFS、未来的健康事件和LLFS参与者的总体健康跨度。

Abstract The Long Life Family Study (LLFS) is a cohort of unusually healthy individuals who show longer health spans and marked delays in the onset of dementia, heart disease and stroke. The LLFS participants also show enrichment in Healthy Aging Phenotypes (HAPs) that include several biological domains such as exceptional memory, grip strength, pulmonary function, blood pressure, and/or metabolism. Since LLFS recruited families showing familial clustering of longevity, even the younger participants may have protective factors that give them increased probability of obtaining exceptional longevity themselves. However, exposure to the SARS-CoV-2 virus may quite possibly be an important risk/protective factor determinant of future health for the LLFS participants. In particular, evidence suggests there may be long term increased CVD risk such as myocarditis and stroke or cognitive impairment in affected survivors. This proposal seeks to augment the existing strengths of LLFS, which include longitudinal detailed phenotyping and serial multi-omics assays to identify risk for various health outcomes by conducting an antibody test for exposure to the SARS-CoV-2 and help classify LLFS participants as symptomatic individuals diagnosed with COVID-19 infection, asymptomatic carriers of COVID- 19 infection, as well as those who did not have COVID-19 infection or the disease. Till date, SARS-CoV-2 antibody studies have focused almost exclusively on blood based antibody responses and mucosal immunity in the naso- and oro-pharyngeal areas, the primary sites of SARS-CoV-2 infection, remain poorly understood. Hence, this study will measure SARS-CoV-2 antibodies in saliva to minimize risk to participants and provide an estimate of mucosal immunity in this population. Specifically, this administrative supplement will measure different isotypes of SARS-CoV-2 antibodies (IgG and IgA) in saliva (Aim 1) and also measure quantitative levels of both these antibody isotypes (Aim 2). We will accomplish both aims by using a self collected saliva sample analyzed using an in-house SARS-CoV-2 ELISA assay and a commercially available FDA-EUA approved assay (Roche Inc.) that will be able to differentiate between SARS-CoV-2 antibodies produced due to natural infection or vaccination. We will use family based multivariate generalized linear models to test for associations of SARS- CoV-2 antibodies (isotypes and quantitative levels) with both aging trajectories as well as with subsequent follow- up data on morbidity and mortality. This approach will allow us to estimate the independent contribution of SARS-CoV-2 antibodies to outcomes of interest, after controlling for other, known risk factors and measures (including various OMICs). Thus, identifying LLFS participants who were exposed to SARS-CoV-2 infection will provide an opportunity to evaluate the effect of SARS-CoV-2 infection on the trajectories of several HAPs that are enriched in LLFS, future health events and overall health span of LLFS participants.