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

在我们之前开发衰老生物标志物特征的基础上，我们将重点放在发现单核细胞中发现的一组新的衰老生物标志物上，单核细胞是一种接近血液的细胞类型，已知随着人类年龄的增长衰老会增加。为了解决量化和靶向衰老单核细胞群体的关键需求，我们结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特征可以预测BLSA的多种特征，包括炎症（IL6， CRP），活动能力和身体健康（握力，步态速度等）以及代谢参数（腰围大小，BMI，血脂等）。独立于协变量如年龄、性别和肾功能，衰老特征改善了对临床结果（如肥胖）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，并表明肥胖与衰老有关，潜在地强调了在进行衰老疗法试验时，除了关注老年人群外，还关注肥胖患者群体的重要性。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.