Characterization of the Intact Proteomic Profile of Senescent-Associated Secretory Phenotype by Top-Down Mass Spectrometry.

Researchers have used an advanced proteomic technique to identify previously unknown intact protein forms and their modifications in the secretions of senescent cells, including potential new biomarkers for aging.

Our bodies contain senescent cells, which are cells that have stopped dividing and are linked to aging and various diseases. These cells release a complex mix of molecules, known as the senescence-associated secretory phenotype (SASP), that can contribute to inflammation and age-related health issues. Historically, studying these secreted proteins has been challenging, as conventional methods often break them down, obscuring their full diversity and structural details.

However, a recent breakthrough involves applying a powerful technique called quantitative top-down mass spectrometry. This innovative approach allows scientists to analyze proteins in their complete, unmodified forms, providing an unprecedented view of their exact structure, including any chemical alterations or variations. Using this method, researchers uncovered a rich array of previously uncharacterized protein forms within the SASP, revealing a much greater complexity than previously understood.

Significantly, the study identified specific modified versions of a protein called HMGA2 as potential indicators of senescence. This deeper, “proteoform-level” understanding of cellular senescence not only highlights the intricate nature of the SASP but also paves the way for discovering new targets for therapies aimed at combating age-related diseases.