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

基于我们先前开发衰老生物标志物特征的努力，我们将努力集中在发现单核细胞中发现的一组新的衰老生物标志物上，单核细胞是一种既接近血液又已知随着人类年龄增长而衰老的细胞类型。为了解决量化和靶向衰老单核细胞群体的关键需求，我们组合了多种方法来开发人类衰老单核细胞特征。我们发现，循环中衰老的单核细胞蛋白质特征预测BLSA的多种性状，包括炎症（IL 6，CRP），活动性和身体健康（握力，步态速度等），以及代谢参数（腰围，BMI，血脂等）。与年龄、性别和肾功能等协变量无关，衰老特征改善了对肥胖等临床结局的预测。这些数据证明了细胞类型特异性衰老特征的预测能力，并表明肥胖与衰老相关，这可能突出了在进行衰老治疗试验时，除了老年人群外，还关注肥胖患者人群的重要性。在正在进行的工作中，我们正在检查GESTALT研究中循环单核细胞衰老特征的预测能力以进行验证。

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.