Translational error in mice increases with ageing in an organ-dependent manner

Area of Science:

• Molecular Biology
• Gerontology
• Biochemistry

Background:

• Protein synthesis accuracy is crucial for cellular function and has been linked to aging.
• Ribosomal errors, or mistranslation, are suspected to increase with age, but direct evidence has been limited.

Purpose of the Study:

• To investigate age-dependent changes in the rate of ribosomal errors.
• To determine if stop-codon readthrough is a sensitive indicator of mistranslation in vivo.

Main Methods:

• Developed a knock-in mouse model with a Kat2-TGA-Fluc reporter for in vivo detection of stop-codon readthrough.
• Utilized fluorescent and bioluminescent imaging for reporter protein expression analysis.
• Assessed reporter gene expression in tissue extracts and whole organs over time.

Main Results:

• Stop-codon readthrough, a measure of translational error, significantly increased with age in mouse muscle (+75%) and brain (+50%).
• No significant age-related increase in stop-codon readthrough was observed in the liver.
• These findings suggest an organ-dependent, age-related increase in protein synthesis errors.

Conclusions:

• The study provides evidence for an age-related decline in translation fidelity.
• Increased stop-codon readthrough with age highlights a potential contributor to the aging process.
• These findings, combined with other research, underscore the importance of protein synthesis accuracy in aging.