Conserved transcriptomic signatures and protein markers in cellular senescence models

Abstract

Abstract Cellular senescence is described as an irreversible cell cycle arrest induced in response to various stresses. Senescent cells are characterised by heterogeneous signalling alterations, complex secretory phenotype, known as senescence-associated secretory phenotype (SASP), and diverse transcriptomic profile. With the aim to investigate senescence heterogeneity and identify conserved transctiptomic alterations and senescence markers, we performed RNA-seq and multiplex proteomic analysis in proteasome inhibition-induced and stress-induced premature senescence models of HFL1 and BJ human fibroblasts. Our data revealed diverse transcriptomic signatures, but also, 231 common differentially expressed genes related to cell division and ECM remodelling, and enriched pathways that remained conserved among the different models with senescence onset. Moreover, we identified a subset of conserved protein senescence markers and validated them in replicative senescent models. These proteins are involved in cell cycle arrest and promote a pro-inflammatory environment in premature and replicative senescence models. We suggest that the simultaneous analysis of p21, p-c-JUN, BCL-xL and survivin in cellular lysates, and IL-8, GM-CSF, GDF-15 and GROa in culture supernatants can provide a powerful tool for the identification and monitoring of senescent cells and can support the assessment of the efficacy of potential senotherapeutic approaches.