Characterization of intact proteomic profile of senescent-associated secretory phenotype (SASP) by top-down mass spectrometry.

Senescent cells are increasingly recognized as major contributors to age-related diseases, primarily through the secretion of bioactive molecules known as the senescence-associated secretory phenotype (SASP). The SASP plays a crucial role in promoting various age-related conditions, including neurodegeneration and type-2 diabetes. While bottom-up proteomic profiling has been instrumental in elucidating senescence heterogeneity and linking SASP factors to aging and obesity, the complexity of protein modifications in SASP remains underexplored. Notably, proteoform-level analysis has not yet been applied to study SASP profiles in detail. In this study, we employ top-down proteomics to capture proteoform diversity in the secretomes of senescent and healthy lung fibroblasts (IMR90).