The power of proteomics to monitor senescence-associated secretory phenotypes and beyond: toward clinical applications.

Introduction: Cellular senescence is a rapidly growing field with potential relevance for the treatment of multiple human diseases. In the last decade, cellular senescence and the senescence-associated secretory phenotype (SASP) have emerged as central drivers of aging and many chronic diseases, including cancer, neurodegeneration, heart disease and osteoarthritis. Major efforts are underway to develop drugs that selectively eliminate senescent cells (senolytics) or alter the SASP (senomorphics) to treat age-related diseases in humans. The translation of senescence-targeting therapies into humans is still in early stages. Nonetheless, it is clear that proteomic approaches will facilitate the discovery of important SASP proteins, development of senescence- and SASP-derived biomarkers, and identification of therapeutic targets for senolytic and senomorphic drugs. Areas covered: We review recent proteomic studies of cellular senescence and their translational relevance and, particularly, characterization of the secretory phenotype and preclinical development of biomarkers (from 2008-2020, PubMed). We focus on emerging areas, such as the heterogeneity of senescent cells and the SASP, extracellular vesicles released by senescent cells, and validating biomarkers of aging in vivo. Expert opinion: Proteomic and multi-omic approaches will be important for the development of senescence-based biomarkers to facilitate and monitor future therapeutic interventions that target senescent cells.