The fountain of youth may not be place, but a protein

Korean scientists may have uncovered a missing link in the biology of aging, potentially opening up a new horizon for unlocking the secret to prolonged youth.

Elderly citizens wait in line for a free lunch service at a public park in Jongno District, central Seoul, on May 12. [NEWS1]

Korean scientists may have uncovered a missing link in the biology of aging, potentially opening up a new horizon for unlocking the secret to prolonged youth.

A team of researchers at KAIST led by Prof. Lee Seung-jae has identified Pelota, a protein involved in ribosome quality control and essential for removing faulty messenger RNA (mRNA), as a key regulator in delaying aging and promoting longevity. The findings are expected to offer new strategies for treating age-related neurodegenerative disorders.

While the deterioration of DNA and proteins in aging cells is known to cause degenerative diseases, the role of RNA in this process has remained unclear until now.

RNA, particularly mRNA, has long been regarded as a transient intermediary in protein synthesis. Its relative instability and short life span have made quantitative analyses and long-term studies difficult, leading to a lack of research into RNA's physiological and functional roles.

Using Caenorhabditis elegans, a nematode commonly used in aging studies due to its short life span, the researchers demonstrated that Pelota is essential for longevity. Overexpressing Pelota in the worms extended their life span, confirming that ribosome-based quality control of defective mRNA is necessary for promoting longevity.

Diagram of the study of the Pelota protein [KAIST]

The study also revealed that ribosomal quality control is linked to both the mechanistic target of the rapamycin (mTOR) signaling pathway — which regulates growth, protein synthesis and autophagy based on nutrient and growth signals — and the autophagy pathway, the cellular process for degrading and recycling damaged components.

The study confirmed that this regulatory mechanism is conserved in mice and humans, with Pelota deficiency linked to muscle aging and symptoms of Alzheimer’s disease. The researchers believe these findings on Pelota and ribosome-based quality control could pave the way for new therapeutic strategies targeting human aging and neurodegenerative diseases.

"While the link between aging and quality control mechanisms at the DNA and protein levels has been well-established, there has been very little molecular evidence that RNA-level quality control systems play a functional role in life span regulation,” said Prof. Lee. “This study presents strong evidence that the removal of defective RNA is a central part of the aging regulatory network.”

The study was published on Aug. 4 in the scientific journal Proceedings of the National Academy of Sciences (PNAS), with Dr. Lee Jong-sun and Dr. Kim Eun-ji of KAIST, Dr. Lee Bo-ra of KRIBB and Dr. Lee Hye-in of Yonsei University as co-first authors.

BY KIM MIN-YOUNG [kim.minyoung5@joongang.co.kr]