KAIST "Controlling Aging Rate Through RNA Regulation... Unveiling the Secret to Longevity"

A team of Korean researchers has identified a key regulator that slows aging and promotes longevity. The researchers expect this discovery to serve as a new turning point for future strategies to treat human aging and degenerative brain diseases.

On August 18, KAIST announced that a collaborative research team led by Professor Seungjae Lee’s group in the Department of Biological Sciences (RNA-Mediated Healthy Longevity Research Center) at KAIST, Professor Jinsoo Seo’s group at Yonsei University, and Dr. Kwangpyo Lee’s group at the Korea Research Institute of Bioscience and Biotechnology (KRIBB), has discovered that the 'PELOTA protein,' which is critical for ribosome quality control, regulates the rate of aging.

Professor Seungjae Lee. Provided by KAIST

The PELOTA protein plays a pivotal role in maintaining translational homeostasis in cells by detecting and resolving errors that occur during the process in which mRNA is translated into protein by ribosomes.

Until now, mRNA was widely regarded as merely an intermediate product for protein synthesis. This is because, compared to DNA, mRNA is less stable and has a shorter lifespan, making quantitative analysis and long-term tracking studies difficult. Due to these limitations, research on the physiological and functional roles of RNA itself has been relatively lacking.

However, the joint research team confirmed that PELOTA, a ribosome quality control factor, plays an essential role in longevity by using Caenorhabditis elegans, a model organism with a short lifespan that is widely used in aging research.

In particular, when PELOTA was overexpressed in normal nematodes, their lifespan was extended, indicating that ribosome-based quality control, which is crucial for removing abnormal mRNA, is necessary for promoting longevity.

The joint research team also revealed that the ribosome quality control system simultaneously regulates the 'mTOR signaling pathway'-a pathway in which cells that are important for aging and energy metabolism in the body sense nutritional status or growth signals to control growth, protein synthesis, and autophagy-and the 'autophagy pathway,' a cellular cleaning and recycling system in which cells break down and recycle unnecessary or damaged components.

According to the joint research team, when PELOTA is deficient, mTOR becomes abnormally activated and autophagy is suppressed, accelerating aging. Conversely, activating PELOTA inhibits mTOR and induces autophagy, thereby maintaining cellular homeostasis and extending lifespan.

Notably, these findings were also conserved in mice and humans, suggesting that PELOTA deficiency may cause muscle aging and Alzheimer's disease.

This indicates that research on PELOTA and ribosome-based quality control could contribute to developing future therapeutic strategies for human aging and degenerative brain diseases.

It is generally known that as aging progresses, the quality of DNA and proteins within cells deteriorates, leading to various degenerative diseases. However, the association between aging and RNA at the molecular level had not been clearly elucidated until now.

Professor Seungjae Lee stated, "While the connection between quality control at the DNA and protein levels and aging has long been established, molecular evidence that RNA-level quality control systems functionally regulate lifespan has been extremely rare. This study provides strong evidence that the removal of abnormal RNA is a core axis of the aging regulatory network."

This research was supported by the National Research Foundation of Korea's Leader Research Program and was jointly conducted by Dr. Jongseon Lee and Dr. Eunji Kim from KAIST, Dr. Bora Lee from KRIBB, and Dr. Hyein Lee from Yonsei University, who served as co-first authors. The results were published on August 4 in the scientific journal 'PNAS.'

This content was produced with the assistance of AI translation services.