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

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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.