Transcriptional upregulation of proteasome activator Blm10 antagonizes cellular aging.

Cellular aging is associated with the damage to DNA, decline in proteasome activity, loss of histones and alteration of epigenetic marks. The atypical proteasome with the activator PA200 in mammals or its ortholog Blm10 in yeast promotes the acetylation-dependent degradation of the core histones during DNA repair or spermiogenesis. We show here that loss of PA200 or Blm10 is the leading cause of the decline in proteasome activity during aging, the latter of which conversely induces the transcription of Blm10. The transcription factor Crt1 suppressed, but the proteasome subunit Rpn4 promoted, the transcription of Blm10. On the contrary to deletion of Rpn4, deletion of Crt1 elevated Blm10 transcription upon DNA damage, reduced core histone levels during aging, and prolonged replicative lifespan. These results suggest that cells can antagonize aging by up-regulating transcription of Blm10, providing important insights into the mechanisms of aging and the aging-related diseases.