Fig. 1.

Human senescence proteostasis decline – molecular features. Proteostasis decline in replicative senescence involves several impairments, including: decline in proteasomal activity, deterioration in the activation of transcriptional stress responses, and diminished nuclear localization of the HSF1 (structure taken from PDB, ID: 5HDG) and ATF6 stress-response transcription factors. Additional changes in the senescent cell chromatin and nucleus that are suggested here to be potentially involved in mediating the proteostasis decline are: formation of senescence-associated heterochromatin foci (SAHF); wide-spread changes in the chromatin modification landscape; and impairment in nuclear integrity, including loss of Lamin B1 (structure taken from PDB, ID: 2KPW).