AsianScientist (Nov. 12, 2025) – As organisms age, the quality of DNA and proteins inside cells declines, which is known to be the cause of various degenerative diseases. However, the connection between ageing and RNA has remained largely unexplored.
Now, Korean researchers have discovered that a ribosome-associated quality control factor, PELOTA, a protein essential for eliminating abnormal mRNA, plays a central role in slowing ageing and promoting longevity.
The findings were published in the Proceedings of the National Academy of Sciences.
All organisms have systems that remove faulty RNA and proteins to maintain cell health. One of these systems, ribosome-associated quality control (RQC), monitors protein production and fixes problems when ribosomes get stuck on defective mRNA.
RQC helps by breaking down faulty proteins, rescuing stalled ribosomes, and degrading defective messenger RNAs (mRNAs). When RQC fails, defective or misfolded proteins accumulate, contributing to the development of neurodegenerative and genetic diseases.
Recent research has shown that RQC becomes even more important with age, helping cells manage the rising number of protein synthesis errors in organisms like yeast and C. elegans, a kind of worm. However, scientists still don’t fully understand how RQC influences lifespan or interacts with other ageing-related pathways.
For the study, the researchers used C. elegans and found that PELOTA is crucial for longevity. Specifically, when PELOTA was overexpressed in normal nematodes, their lifespan increased, indicating that ribosome-associated quality control mechanisms involved in eliminating abnormal mRNA are vital for enhancing longevity.
The research also indicated that the RQC system concurrently regulates both the mTOR signaling pathway, which detects nutrient availability or growth signals to manage cell growth, protein synthesis, and the autophagy pathway, which serves as the cellular cleanup and recycling mechanism, allowing cells to decompose and repurpose unnecessary or damaged components.
When there was a deficiency of PELOTA, the mTOR pathway became abnormally activated, leading to a suppression of autophagy and accelerating the ageing process. In contrast, the activation of PELOTA inhibited mTOR activity and promoted autophagy, which helped to maintain cellular balance and prolong lifespan.
The scientists noted that this mechanism is preserved in both mice and humans. The research also indicated that the absence of PELOTA may contribute to muscle ageing and the development of Alzheimer’s disease, underscoring its significance in age-related conditions.
These results suggest that investigating PELOTA and ribosome-associated quality control could be crucial for creating therapeutic approaches aimed at addressing human ageing and neurodegenerative disorders.
The research is also significant because, till now, RNA, especially mRNA, has typically been viewed as a temporary intermediary in the process of protein synthesis. Its lack of stability has complicated quantitative studies and tracking over time, resulting in its physiological and functional roles not being much explored compared to DNA.
“While the connection between quality control and ageing has been well established at the DNA and protein levels, molecular evidence showing that RNA quality control also functionally contributes to lifespan regulation has been very limited,” said Seung-Jae V. Lee, lead researcher and professor, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST).
He emphasized that the “study provides strong evidence that the removal of abnormal RNA is a central axis in the aging regulatory network.”
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Source: Korea Advanced Institute of Science and Technology; Image: nobeastsofierce/shutterstock
The study can be found at Pelota-mediated ribosome-associated quality control counteracts aging and age-associated pathologies across species
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