Effect of heat-shock on transcriptome- and proteome-wide stress responses of human IMR-90 fibroblasts in different proliferation states.

However, most of our understanding of human cell stress responses stems from experiments in rapidly-dividing cell culture models. Here, we used primary human diploid fetal lung fibroblasts (IMR-90) in proliferating, contact-inhibited quiescent, or doxorubicin-induced senescent states, to explore their responses to a severe heat-shock (44 degrees Celsius for 2 hours) at the transcriptome, proteome, poly-ubiquitylated proteome, and insoluble proteome levels.

We identify remarkable conservation in stress responses at the transcriptome, proteome, and poly-ubiquitylated proteome levels, albeit with slight dampening in the magnitude of changes in both quiescent and senescent state. By contrast, there was a considerable impairment in stress-induced sedimentation of RNA-binding proteins in the senescent state, several of which are linked to neurodegenerative disease pathology. We propose a senescence-specific divergence in proteostasis strategies at the level of stress-induced protein and RNA granule formation, which could contribute to the frailty associated with senescent-cell accumulation in ageing and disease.