KAIST Discovers Protein That Plays Key Role in Preventing Aging and Extending Lifespan

A protein that plays a key role in preventing aging and extending lifespan has been discovered. This finding is expected to provide important clues for uncovering the mechanisms of aging and developing strategies to treat age-related diseases.

On March 18, KAIST announced that a research team led by Professor Seungjae Lee from the Department of Biological Sciences, in collaboration with Professors Yoonki Kim and Kwangrok Lee from the same department, has found that the enzyme 'RNASEK', which degrades circular RNA, plays a crucial role in slowing aging and increasing lifespan.

Research has found that the protein RNASEK, an enzyme that degrades circular RNA, plays a crucial role in slowing aging and extending lifespan. KAIST (AI-generated image)

Until now, circular RNA was believed to be highly stable, accumulating in cells with age and serving merely as a 'biomarker of aging'. The molecular mechanisms for removing RNA and its direct association with aging had not been clearly identified.

With this in mind, the joint research team conducted a study to determine how the accumulation of circular RNA affects aging and whether there is an internal cellular management system that regulates this process.

The researchers began with experiments using the nematode Caenorhabditis elegans, widely used in aging studies due to its short lifespan. Through these experiments, the team confirmed that the RNA-degrading enzyme RNASEK protein is essential for longevity, and found that as aging progresses, the amount of RNASEK decreases, resulting in abnormal accumulation of circular RNA within the cells.

Conversely, artificially increasing (overexpressing) the amount of RNASEK extended lifespan and prolonged healthy survival. This indicates that the proper removal of circular RNA within the cell is vital for maintaining longevity and good health.

The study also revealed that the RNASEK protein prevents the aggregation of circular RNA, which can otherwise form toxic clusters.

When RNASEK protein is deficient, circular RNA accumulates excessively, abnormally forming masses called 'stress granules' within the cells. This process impairs cellular function and can accelerate aging.

From another perspective, the RNASEK protein works together with the chaperone protein 'HSP90' (a protein that assists in proper folding and prevents aggregation of other proteins) to inhibit the formation of these stress granules, thereby helping maintain normal cellular function. In other words, the interaction between RNASEK and HSP90 can slow down aging in the human body.

(Back row from left) Professors Yoonki Kim, Seungjae Lee, and Kwangrok Lee from KAIST, (front row from left) Drs. Sungho Boo, Sieun Kim, and Seokjin Ham, (top) Dr. Donghoon Lee. KAIST

Notably, these phenomena were observed not only in Caenorhabditis elegans, but also in mice and human cells. In mammals as well, RNASEK directly degrades circular RNA. In both human cells and mouse models, a deficiency of RNASEK led to signs of premature aging.

The joint research team emphasized the significance of this study in elucidating an RNA-level regulatory mechanism of aging. They also suggested that research using RNASEK to control circular RNA could serve as a foundation for developing future strategies to treat human aging and degenerative diseases.

Professor Seungjae Lee explained, "Until now, circular RNA was considered merely a 'biomarker of aging' that accumulates due to its high stability. However, our study demonstrates that circular RNA accumulating with age actually induces aging, and that RNASEK, which removes it, acts as a key regulator that slows aging and promotes healthy longevity."

Meanwhile, Drs. Sieun Kim, Seokjin Ham, Sungho Boo, and Donghoon Lee from the Department of Biological Sciences at KAIST participated as co-first authors in this research. The results of the study (paper) were published in the international scientific journal 'Molecular Cell' on February 24.

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