For decades, circular RNA was treated as little more than molecular background noise — stable fragments that accumulated in aging cells but appeared to cause no particular harm. Scientists noted the buildup, logged it as a marker of getting older, and largely moved on.
A team at KAIST has now found reason to reconsider. Their research identifies a specific enzyme responsible for clearing this RNA, and the evidence suggests the accumulation isn’t simply a sign of aging — it may be actively driving it.
Circular RNA: from harmless byproduct to aging suspect
Circular RNA has an unusual property: unlike most RNA molecules, which break down relatively quickly after serving their purpose, circular RNA resists degradation almost entirely. It lacks the structural endpoints that cellular machinery typically targets, so it simply persists — accumulating inside cells over years and decades. Scientists noticed this buildup and, for a long time, treated it as a passive feature of aging. A molecular footnote rather than a cause.
That classification is now under pressure. When circular RNA builds up beyond a certain threshold, it begins to clump into structures called stress granules — dense aggregates that obstruct the movement of proteins and signals within the cell. The KAIST research suggests this isn’t merely incidental. These granules impair function and, the evidence indicates, accelerate the aging process itself.
Enter RNASEK: the enzyme that takes out the trash
To understand how circular RNA is normally kept in check, the KAIST team ran a genetic screen targeting ribonucleases — enzymes whose job is to cut and degrade RNA. One enzyme emerged as the key player: RNASEK,, a ribonuclease capable of specifically cleaving circular RNA and clearing it from the cell.
RNASEK levels don’t stay constant. The enzyme naturally declines as organisms age, which helps explain why circular RNA accumulates in the first place — not because cells suddenly produce more of it, but because the disposal system gradually loses capacity. The research also found that RNASEK works alongside HSP90, a chaperone protein that helps prevent misfolding and clumping. When either component falters, the cellular environment begins to deteriorate.
Longer, healthier lives — at least in the lab
The most striking results came from experiments with C. elegans, the small roundworm that has become a standard model in aging research. When the team artificially increased RNASEK expression, the worms didn’t just live longer — they remained healthier for more of that extended lifespan. The intervention improved what researchers call healthspan, not only lifespan.
The mechanism didn’t appear to be a quirk of worm biology. Mammalian RNASEK was also shown to directly degrade circular RNA, suggesting the pathway is evolutionarily conserved rather than species-specific — a detail that matters, because it implies the same basic logic applies across very different organisms. Going in the opposite direction confirmed the picture: reducing RNASEK in human cells and mouse models led to signs of premature aging, consistent with the idea that maintaining the enzyme’s activity is protective.
From worms to humans: what comes next
Published in Molecular Cell, the study carries a broader conceptual implication. Aging research has long centered on DNA damage and protein aggregation as the primary mechanisms of cellular decline. This finding adds another dimension: RNA management. Specifically, it suggests that failing to clear a particular class of RNA molecule may be a meaningful driver of how quickly cells deteriorate.
No therapy that boosts RNASEK in humans currently exists. Translating findings from roundworms and cell cultures into clinical treatments is a long and uncertain process, and the researchers haven’t claimed otherwise. What the study does provide is a concrete molecular target — a specific enzyme with a defined role, whose activity can in principle be measured, modulated, and potentially restored.
The researchers suggest that controlling circular RNA clearance could inform strategies for treating degenerative diseases, not only for extending lifespan in otherwise healthy individuals. If the pathway holds up under further scrutiny, the question shifts from whether RNASEK matters to whether it can be reliably engaged in human biology. That work is now the frontier — and it begins with the knowledge that the target exists.