Study Finds Removing Circular RNA Slows Aging and Extends Lifespan

A team at KAIST has uncovered that clearing certain RNA molecules known as circular RNAs from cells can slow aging and support longer life. Their work, published in Molecular Cell, offers new insight into how aging occurs at the molecular level and suggests ways to design therapies for age-related diseases.

The team, led by Professor Seung-Jae V. Lee, identified a protein enzyme called RNASEK that breaks down circular RNA. They found that RNASEK plays an essential role in regulating lifespan by preventing circular RNA from accumulating as organisms grow older.

Circular RNA has long been seen as a byproduct or marker of aging because of its structural stability, which allows it to build up in cells. However, how this process connects to aging had not been clearly understood. Using the model organism Caenorhabditis elegans (C. elegans), a roundworm commonly used in longevity research, the team revealed that RNASEK activity declines with age. As RNASEK levels fall, circular RNA increases, leading to cellular dysfunction.

When the researchers enhanced RNASEK expression, the worms lived longer and remained healthy, demonstrating that the active removal of circular RNA is vital for sustaining normal cell function. The team also showed that RNASEK suppresses the toxic aggregation of circular RNA that can form “stress granules” inside aged cells. These granules disrupt normal processes and accelerate decline. RNASEK works with another protein, HSP90, to prevent these stress granules from forming and to maintain stable cellular conditions.

Importantly, similar effects were observed in human cells. In mammals, RNASEK directly degrades circular RNA, and its deficiency in human or mouse cells led to signs of premature aging. According to Professor Lee, “This study proves that circular RNA accumulated during aging actually induces aging, and that RNASEK, which removes it, is a key regulator that slows aging and induces healthy longevity.”