Clearing circular RNA slows aging, extends lifespan, KAIST study finds

A Korean research team has demonstrated that targeting and removing circular RNA can slow aging and extend lifespan.

The Korea Advanced Institute of Science and Technology (KAIST) said Wednesday that researchers led by Professors Lee Seung-jae, Kim Yoon-ki, and Lee Gwang-rog from the Department of Biological Sciences found that RNASEK, an enzyme that degrades circular RNA, plays a key role in regulating aging and longevity.

Circular RNA has been known primarily as a stable marker of aging, as it accumulates in cells over time. However, the mechanisms linking its removal to aging have remained unclear.

The research team investigated how the accumulation of circular RNA affects aging and whether intracellular regulatory systems control it.

A KAIST research team has discovered that removing circular RNA can slow aging and extend lifespan. Pictured (back row, from left) are Professors Kim Yoon-ki, Lee Seung-jae, and Lee Gwang-rog. Front row (from left): Boo Seong-ho, Kim Sie-un, and Ham Seok-jin. Top: Lee Dong-hoon. (Courtesy of KAIST)

Using the nematode C. elegans—a model organism widely used in aging research due to its short lifespan—the team found that RNASEK is essential for longevity. As aging progresses, RNASEK levels decrease, leading to abnormal accumulation of circular RNA within cells.

Conversely, increasing RNASEK expression extended lifespan and helped maintain health during aging, suggesting that proper removal of circular RNA is critical for longevity.

The study also showed that RNASEK prevents circular RNA from aggregating and becoming toxic. When RNASEK is deficient, accumulated circular RNAs form abnormal clusters known as “stress granules,” which impair cellular function and accelerate aging.

RNASEK works with the chaperone protein HSP90—which prevents protein misfolding and aggregation—to suppress stress granule formation and maintain cellular stability. This mechanism was observed in C. elegans, as well as in mouse and human cells. In mammals, RNASEK also directly degrades circular RNA, and its deficiency led to signs of premature aging in both human cells and mouse models.

The researchers said the study is significant because it identifies a direct functional role of circular RNA in aging, rather than it being merely a biomarker, and highlights RNASEK as a potential therapeutic target. They suggested that modulating circular RNA could open new avenues for treating aging-related and degenerative diseases.

“Previously, circular RNA was considered mainly a marker that accumulates with age due to its stability,” said Professor Lee Seung-jae. “Our study shows that this accumulation actively drives aging, and that RNASEK plays a crucial role in promoting healthy longevity by removing it.”

Ham Seok-jin, Boo Seong-ho, and Lee Dong-hoon from KAIST served as co-first authors of the study. The findings were published in the journal Molecular Cell under the title, “Ribonuclease κ promotes longevity by preventing age-associated accumulation of circular RNA in stress granules.”