271 Ribosome heterogeneity by rRNA methylation in skin cell senescence

The accumulation of senescent cells is associated with several age-related pathologies and represents a primary driver skin aging. Senescence cause tissue damage by secreting mix pro-inflammatory cytokines extracellular matrix remodeling factors. This study aims to elucidate how ribosomes protein translation change in cellular senescence. Particularly we focus on alterations the methylation patterns ribosomal RNA. We exposed human dermal fibroblasts doxorubicin induce senescence tested if specific methylations RNA contribute phenotype. also measured total synthesis OPP incorporation senescence-associated mRNAs polysome profiling. Global synthesis, ribosome biogenesis, nucleolar size surprisingly increased compared contact-inhibited quiescent cells. Furthermore, differentially methylated sites, either hyper- or hypo-modified, were present rRNA proliferating Methylation levels showed correlation expression snoRNAs installing these modifications. By inhibiting snoRNAs, confirmed causality modifications for promoting cell proliferation. Our combined data suggest that even subtle might have profound precise effects physiology heterogeneity ribosomes. Ribosomal provide future targets selective elimination blocking their harmful secretome.