Mapping the heterogeneity of the human senescent proteome

Abstract

Cellular senescence is a unique response to sublethal stress characterized by at least two elements: persistent cell cycle arrest and a senescence-associated secretory phenotype (SASP). Recent evidence suggests a close link between senescence and aging, as selective elimination of senescent cells in mice improves longevity and overall health. Therefore, there is increased interest in identifying markers to develop drugs (senolytics) that selectively eliminate senescent cells without harming healthy, proliferating cells. However, senescent phenotypes vary across cell types and inducers, creating a need for tissue-specific markers of senescence. To this “senescence catalog” has three aims: 1) Identify protein and RNA markers of senescence; 2) Compare across models to find overlapping markers; and 3) Validate markers with scRNA-seq and IHC in culture and in mice.