Published on: Aug 18, 2025
As we age, the integrity of DNA and proteins in our cells gradually deteriorates, contributing to the onset of degenerative diseases. While this link between aging and DNA/protein damage has been researched extensively, the role of RNA in aging has remained largely elusive. Now, a team of Korean researchers has identified a pivotal RNA-regulating protein—PELOTA—that slows aging and promotes longevity, opening new avenues for anti-aging and neurodegenerative disease therapies.
KAIST (President Kwang Hyung Lee) announced that a joint research team led by Professor Seung-Jae V. Lee of KAIST's Department of Biological Sciences; Professor Jinsoo Seo of Yonsei University; and Professor Kwang-Pyo Lee of the Korea Research Institute of Bioscience and Biotechnology (KRIBB), under the National Research Council of Science & Technology (NST), has revealed that PELOTA—a ribosome-associated quality control protein responsible for eliminating faulty mRNA—plays a critical role in regulating the aging process.
Traditionally, mRNA has been considered a short-lived molecule that merely serves as a messenger in protein production. Due to its instability, studying its long-term role in physiological processes has been challenging, leaving its impact on aging mostly unexplored compared to DNA.
Using the model organism C. elegans, known for its utility in aging research, the team demonstrated that PELOTA is essential for longevity. Overexpressing this protein extended the worms’ lifespan, indicating that ribosome-associated quality control—specifically, the removal of aberrant mRNA—is a key driver of longevity.
The researchers also uncovered that this quality control mechanism coordinates two critical cellular pathways: the mTOR signaling pathway, which regulates growth and metabolism, and autophagy, the process of recycling damaged cellular components. In the absence of PELOTA, mTOR activity increased abnormally while autophagy declined, speeding up aging. Conversely, activating PELOTA suppressed mTOR, enhanced autophagy, helped maintain cellular balance, and ultimately prolonged lifespan.
Importantly, the team observed that this mechanism is conserved in both mice and humans. They found that loss of PELOTA function may contribute to muscle aging and Alzheimer’s disease, highlighting its potential role in combating age-related disorders.
These findings suggest that ribosome-associated RNA quality control is a crucial, previously underappreciated component of aging biology—and a promising target for future therapeutic strategies aimed at aging and neurodegenerative diseases.
Commenting on the research, Professor Seung-Jae V. Lee remarked, Quality control at the DNA and protein levels has long been linked to aging, but molecular evidence of RNA quality control influencing lifespan has been scarce. Our study clearly demonstrates that eliminating abnormal RNA is a vital part of the aging regulatory system.
Source: https://news.kaist.ac.kr/newsen/html/news/?mode=V&mng_no=50590
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