Circulating cell type senescence signatures track distinct dimensions of health status and trajectories in human longitudinal cohorts

Cellular senescence is implicated in age-related pathologies, and identifying circulating biomarkers of senescence holds great diagnostic potential. Circulating senescence signatures are predictive of age-related traits and diseases, though cell type senescence signatures have not been comprehensively explored. In this study, senescence signatures from the Senescence Catalog (SenCat), including 14 human cell types are examined in circulation for clinical relevance in two longitudinal studies-1,275 participants of the Baltimore Longitudinal Study of Aging (BLSA) and 997 participants of the Invecchiare in Chianti (InCHIANTI) study. Notably, pooled senescence proteins outperform non-senescence proteins in predicting many clinical parameters such as age and hypertension, and in many instances, cell type senescence signatures map most strongly to their corresponding health domain. Importantly, the immune cell senescence signature is associated with mortality and future disease onset. This study demonstrates that circulating cell type biomarkers of senescence can reveal higher resolution health status than previously attained.