The burden of lingering senescent cells grows with age in tissues throughout the body. Cells enter the senescent state constantly, but the pace of clearance of senescent cells by the immune system falters with advancing age. Senescent cells secrete a mix of pro-inflammatory, pro-growth signals that are disruptive to tissue structure and function when sustained for the long term. Analysis of circulating molecules in a blood sample can in principle be used to measure the body-wide burden of senescent cells, though no strong consensus approach has emerged yet from the various methods demonstrated in recent years. Here, find another contender for that consensus approach, where researchers use proteomic assessment of blood samples to build a score based on the strength of senescent cell signaling, and find that this score correlates with mortality risk.
The accumulation of senescent cells is a recognized hallmark of biological aging and is associated with the onset of multiple chronic medical conditions. Senescent cells exhibit a distinct secretory profile, known as the senescence-associated secretory phenotype (SASP), which can propagate cellular senescence to neighboring and distant tissues. Measuring SASP factors in blood serves as a practical proxy for cellular senescence burden and may help track disease states and intervention outcomes.
We developed and validated a composite SASP Score by integrating large-scale population proteomics data with a semi-supervised deep learning framework. The analytical workflow included: (1) selection of biologically curated SASP proteins; (2) development of a Guided autoencoder with Transformer (GAET) model using data from the UK Biobank Pharma Proteomics Project (UKB-PPP); (3) internal evaluation and association analyses within the UK Biobank; and (4) external validation and longitudinal assessment in an independent randomized clinical trial cohort.
The deep learning-based SASP Score was a strong, independent predictor of mortality risk and incident serious, chronic medical conditions (e.g., dementia, COPD, myocardial infarction, stroke). In an independent cohort, multimodal exercise significantly changed the SASP Score trajectory over 18 months.
