Translational changes upon aging and dietary restriction in progeroid DNA-repair-deficient mice [Ribo-Seq]

We showed recently that with aging time- and exposure-dependent accumulation of DNA damage derails the basal process of transcription physically stalling RNA polymerase, lowering and skewing the transcriptional landscape in a gene-length-dependent fashion. However, how this influences the translational output and whether translation is similarly affected is largely unknown.

Here, we present a parallel analysis of transcriptional and translational liver profiles from the well-characterized Ercc1Δ/− progeroid, DNA repair-deficient mouse model compared to wildtype under ad libitum conditions and upon dietary restriction (DR), which strongly delays aging in this mutant. Using ribosome profiling, we found that transcriptional changes during accelerated, normal, and delayed aging are largely preserved at the translational level ruling out a major translational impact on gene expression in aging in our models.