Summary: Researchers discovered a biological “trash disposal” mechanism that directly controls how fast we age. While circular RNA has long been known to accumulate in cells as we get older, this study proves for the first time that this buildup isn’t just a side effect of aging—it actually causes it. By identifying the enzyme RNASEK, which degrades this aging-linked RNA, scientists have found a way to potentially reset the cellular clock.
Key Facts
- The “Toxic” Buildup: Circular RNA is uniquely stable, meaning it doesn’t break down easily. As we age, it piles up inside cells, eventually clumping into harmful “stress granules” that impair cellular function.
- The Discovery of RNASEK: The team identified RNASEK as the specific enzyme responsible for degrading circular RNA. As organisms age, levels of this enzyme naturally drop, leading to RNA “traffic jams.”
- Lifespan Extension: In experiments with C. elegans (roundworms), artificially increasing RNASEK levels (overexpression) significantly extended healthy lifespan.
- The Chaperone Connection: RNASEK doesn’t work alone; it partners with a protein called HSP90 to prevent these RNA clumps from becoming toxic.
- Cross-Species Evidence: This mechanism was confirmed in both human cells and mouse models. When RNASEK was deficient in human cells, it led to signs of premature aging.
- Therapeutic Potential: Controlling RNASEK to clear out circular RNA could become a primary strategy for treating degenerative diseases and slowing human aging.
Source: KAIST
Cells in our bodies produce RNA based on genetic information stored in DNA, and RNA serves as a blueprint for making proteins. Researchers at our university have discovered a new phenomenon: removing ‘circular RNA’ that accumulates in cells as we age can slow down aging and extend lifespan. This study provides crucial clues for uncovering the principles of aging and developing treatment strategies for related diseases.
Professor Seung-Jae V. Lee’s research team (RNA-Mediated Healthspan and Longevity Research Center) from the Department of Biological Sciences, in collaboration with research teams led by Professors Yoon Ki Kim and Gwangrog Lee, announced on the 18th that they discovered the RNASEK protein—an enzyme that degrades circular RNA—plays a vital role in slowing aging and extending lifespan.
Until now, circular RNA has been regarded mainly as an aging marker because of its stability, which allows it to accumulate over time. However, the molecular mechanism for removing this RNA and its direct link to aging had not been clearly identified. The research team conducted this study to determine how the accumulation of circular RNA affects aging and whether an intracellular management system exists to regulate it.
Using Caenorhabditis elegans (C. elegans), a short-lived roundworm widely used in aging research, the team first confirmed that the circular RNA-degrading enzyme RNASEK is essential for longevity. They also discovered that as aging progresses, the amount of RNASEK decreases, resulting in an abnormal accumulation of circular RNA within cells.
Conversely, artificially increasing the levels of RNASEK (overexpression) extended the lifespan and allowed the organisms to survive longer in a healthy state. This implies that the process of appropriately removing cellular circular RNA is critical for maintaining health and longevity.
The research team also found that RNASEK prevents the toxic aggregation of circular RNAs in aged organisms. . When RNASEK is deficient and circular RNA accumulates, “stress granules” form abnormally inside the cell, which can impair cellular functions and accelerate aging.
RNASEK works alongside the chaperone protein HSP90 (which helps proteins avoid misfolding or clumping) to inhibit the formation of these stress granules and help cells maintain a normal state. Notably, this phenomenon was observed not only in C. elegans but also in human cells. In mammals, RNASEK also functions to directly degrade circular RNA; a deficiency of RNASEK in human cells and mouse models led to premature aging.
The researchers explained that this study is significant as it identifies a mechanism for regulating aging at the RNA level. They suggested that research using RNASEK to control circular RNA could lead to the development of treatment strategies for human aging and degenerative diseases.
Professor Seung-Jae V. Lee of KAIST, who led the study, explained, “Until now, circular RNA was merely regarded as a marker of aging that accumulates over time due to its stability. 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.”
Drs. Sieun S. Kim, Seokjin Ham, Sung Ho Boo, and Donghun Lee from the KAIST Department of Biological Sciences participated as joint first authors.
The research results were published on February 24 in the world-renowned scientific journal Molecular Cell.
Funding: This research was conducted with support from the Leader Researcher Program of the National Research Foundation of Korea.
Key Questions Answered:
A: Think of circular RNA like clutter in a house. A little bit is fine, but because it’s so stable, it never “goes out with the trash.” Over decades, this clutter turns into massive piles (stress granules) that block the hallways of the cell, stopping vital proteins and signals from getting where they need to go. This “cellular hoarding” eventually leads to cell death and aging.
A: Not yet. While the study found that increasing RNASEK extends life in lab models, we are still in the early stages of translating this to humans. However, this discovery gives pharmaceutical researchers a specific target. Instead of just treating the symptoms of aging, we might one day have treatments that “re-activate” the RNASEK disposal system to keep cells clean.
A: C. elegans are the “gold standard” for aging research because they live for only about 2–3 weeks, but share many of the same genetic pathways as humans. This allows scientists to see the entire aging process—and the effects of life-extending interventions—in a matter of days rather than years.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this genetics and longevity research news
Author: JEEHYUN LEE
Source: KAIST
Contact: JEEHYUN LEE – KAIST
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Ribonuclease κ promotes longevity by preventing age-associated accumulation of circular RNA in stress granules” by Sieun S. Kim, Seokjin Ham, Sung Ho Boo, Donghun Lee, Hyemin Min, Eunseok Kang, Rosa Haque, Hanseul Lee, Yoonji Jung, Sujeong Kwon, Sangsoon Park, Hae-Eun H. Park, Eun Ji E. Kim, Wooseon Hwang, Eunah Kim, Gee-Yoon Lee, Kun-Young Park, Jae Myoung Suh, Gwangrog Lee, Yoon Ki Kim, and Seung-Jae V. Lee. Molecular Cell
DOI:10.1016/j.molcel.2026.01.031
Abstract
Ribonuclease κ promotes longevity by preventing age-associated accumulation of circular RNA in stress granules
Circular RNAs (circRNAs) accumulate with age, but their functional impact on aging remains elusive.
In this study, we reveal a mechanism by which ribonuclease κ (RNASEK) prevents age-dependent circRNA accumulation by promoting its degradation. Through a genetic screen targeting ribonucleases, we identified RNASEK as a specific circRNA-cleaving ribonuclease.
RNASEK is downregulated during aging, causing the age-dependent increase in circRNA levels. RNASEK is necessary and sufficient for lifespan extension and healthspan maintenance in Caenorhabditis elegans.
Mammalian RNASEK also directly degrades circRNAs and is required for preventing premature aging in cultured human cells and mice, indicating its evolutionarily conserved role.
Notably, we demonstrate that circRNAs localize within stress granules, where RNASEK, in collaboration with heat shock protein 90 (HSP90), prevents the toxic aggregation of circRNAs in aged organisms.
Our study establishes RNASEK as a conserved regulator of aging and offers a strategy for targeting circRNAs to mitigate age-associated diseases and to extend organismal healthspan.
