Single-cell quantification of senescence burden reveals cell type-specific ageing dynamics across organs

Abstract

Abstract Cellular senescence, a hallmark of ageing, drives tissue dysfunction by promoting inflammation and fuelling disease. Yet, the dynamics of senescent cell accumulation across tissues and their cell type identity remain poorly understood. Here, we introduce the first, single-cell, protein-level approach, combining multiple senescence markers for the identification and quantification of senescent cells across multiple tissues in mice and in human PBMCs. Applying this method, we reveal widespread but heterogeneous changes in senescence marker expression across cell types and tissues. The cells we identify as senescent displayed transcriptomic senescence signatures, providing a direct molecular link between protein- and mRNA-level detection of senescence. Importantly, senescence accumulation was strongly coordinated within organs but showed little correlation across them, supporting the idea of a tissue specific progression of ageing. These findings refine our understanding of the tissue-specific dynamics of senescence accumulation with age, and provide a framework for evaluating diverse therapeutic interventions.