Translation error rates increase during aging in post-mitotic cells
A preprint identifies tRNA pool remodeling as a key driver of rising protein synthesis errors in aging yeast and mouse cells.
In a new preprint, researchers analyzed proteome-wide translation error frequencies across yeast and mice using mass spectrometry. The team evaluated how amino acid misincorporation varies across tissues and with age. They found that translation fidelity is specific to both the organism and the organ. Error rates correlated with codon-anticodon pairing thermodynamics and tRNA pool composition. Furthermore, most identified protein errors imposed a negative fitness burden. During aging, protein error frequencies increased specifically in post-mitotic cells, whereas mitotic cells showed no such rise. These fidelity declines correlated with shifts in the tRNA pool, highlighting tRNA remodeling as a crucial regulator of translation accuracy over the lifespan.
Why it matters
Protein errors contribute to misfolding and cellular dysfunction. Showing that translation errors selectively accumulate in aged post-mitotic cells clarifies how translational fidelity changes over the lifespan.
Caveats
The study has been released as a preprint and has not yet completed peer review. Additionally, the research was conducted strictly in yeast and mouse systems rather than human subjects.
The paper
Translation fidelity mechanisms and their changes in aging
Aguilar Rangel M, Powers C, Lee J et al.
bioRxiv · 25 Sep 2026 · Preprint, not yet peer-reviewed