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  3. Ribosome Molecular Aging Shapes Translation Dynamics.
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  3. Ribosome Molecular Aging Shapes Translation Dynamics.

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Ribosome Molecular Aging Shapes Translation Dynamics.

Jordy F Botello1, Lifei Jiang1, Peter J Metzger1

  • 1Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.

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|March 27, 2026

View abstract on PubMed

Summary
This summary is machine-generated.

Cellular aging affects protein production. Older ribosomes, the cell's protein-making machinery, show impaired function, leading to translation errors and impacting organismal aging.

Keywords:
PROTACsagingchemogeneticsepitranscriptomicsorganelle proteomicspulse chaseribosomeribosome profilingtranslation

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Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Aging Research

Background:

  • Cellular homeostasis requires component renewal, but some complexes like ribosomes have long lifespans.
  • The functional impact of extended molecular age on cellular components, particularly ribosomes, remains unclear.

Purpose of the Study:

  • To develop a method for mapping the life stages of biomolecules within cells.
  • To investigate how the age of ribosomes affects their function and translational dynamics.

Main Methods:

  • Developed a spatiotemporal mapping strategy to track ribosome age and location.
  • Analyzed ribosome function, including elongation, pausing, and termination, based on molecular age.
  • Profiled ribosomal RNA modifications to assess age-related changes.
  • Utilized pulse-chase labeling in *C. elegans* to study ribosome aging *in vivo*.

    • Main Results:

    • Intracellular ribosome aging alters translational dynamics for specific transcripts.
    • Aged ribosomes show impaired elongation at basic amino acid-rich sequences, causing pausing and premature termination.
    • Molecular aging increases ribosome collision propensity in specific subpopulations.
    • Enrichment of aged ribosomes amplifies age-dependent translation defects.
    • *In vivo* studies in aged *C. elegans* confirmed aged ribosomes influence translational dynamics during organismal aging.

    Conclusions:

    • Ribosome molecular age is a key determinant of translational dynamics.
    • Aging of ribosomes, a core gene-expression complex, is linked to organismal aging.
    • The developed pulse-chase strategy maps macromolecular demographics in space and time.