Development of Sensitive and Specific Proteomic Biomarkers of Aging, Health, Frailty, and Morbidity in Human Cohorts

开发人类群体中衰老、健康、虚弱和发病的敏感和特异性蛋白质组生物标志物

基本信息

批准号：
10913040
负责人：
Nathan Basisty
金额：
$ 5.7万
依托单位：
NATIONAL INSTITUTE ON AGING
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10913040
关键词：
Address Adipocytes Age Aging Biological Biological Aging Biological Markers Blood Body mass index Cells Circulation Clinical Collection Coupled Data Development Disease Elderly Epithelial Cells Fibroblasts Future Gait speed Gender Geroscience Hand Strength Health Human IL6 gene Immune Individual Inflammation Lipids Longevity Longitudinal Studies Lymphocyte Measurement Measures Mediating Metabolic Modeling Molecular Molecular Profiling Morbidity - disease rate Mus Myoblasts Obesity Outcome Pathology Phenotype Plasma Population Proteins Proteome Proteomics Renal function Serum Solid Testing Tissues Work aging population biomarker signature blood-based biomarker cell type circulating biomarkers cohort frailty improved innovation minimally invasive monocyte mortality multiple chronic conditions novel novel marker obese patients patient population physical conditioning predict clinical outcome proteomic signature senescence theories tool trait treatment strategy validation studies

项目摘要

Building on our previous efforts to develop senescence biomarker signatures, we have focused our efforts on the discovery of a novel set of senescence biomarkers found in monocytes, a cell type that is both proximal to the blood and known to increase in senescence with age in humans. To address the critical need to quantify and target senescent monocyte populations, we have combined multiple approaches for the development of senescent monocyte signatures in humans. We found that senescent monocyte protein signatures in circulation predict multiple traits in BLSA, including inflammation (IL6, CRP), mobility and physical health (grip strength, gait speed, etc), and metabolic parameters (waist size, BMI, lipids, etc). Independent of covariates such as age, gender, and kidney function, the senescence signatures improve the prediction of clinical outcomes such as obesity. These data demonstrate the predictive power of cell type specific senescence signatures, and suggest that obesity is associated with senescence, potentially highlighting the importance of focusing on obese patient populations in addition to aged populations when conducting trials of senotherapuetics. In ongoing work, we are examining the predictive power of senescence signatures in circulating monocytes from the GESTALT study for validation.

在我们先前开发衰老生物标志物特征的努力的基础上，我们将精力集中在发现单核细胞中发现的一套新型衰老生物标志物上，这种细胞类型既靠近血液，又已知会随着人类年龄的增长而闻名。为了满足量化和靶向衰老单核细胞种群的关键需求，我们结合了多种方法来发展人类衰老单核细胞特征。我们发现，循环中的衰老单核细胞蛋白特征可以预测BLSA中的多种特征，包括炎症（IL6，CRP），迁移率和身体健康（抓地力强度，步态速度等）和代谢参数（腰围，BMI，BMI，脂质等）。与年龄，性别和肾功能等协变量无关，衰老特征可以改善肥胖症等临床结果的预测。这些数据证明了细胞类型特异性衰老特征的预测能力，并表明肥胖症与衰老有关，可能突出了在进行鼻痛试验时，除了老年人群外，还要强调关注肥胖患者人群的重要性。在正在进行的工作中，我们正在研究Gestalt研究中循环单核细胞中衰老特征的预测能力。