Molecular cellFeb 26, 2026

Ribonuclease K helps extend lifespan by stopping buildup of circular RNA in stress-related cell structures as we age

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

RNASEK appears to protect aging cells and organisms by clearing circular RNAs from stress granules.

Evidence

A preclinical genetic and mechanistic study used a ribonuclease screen plus C. elegans, cultured human-cell, and mouse experiments to test RNASEK control of circRNAs and aging phenotypes.

Caveat

The work is mechanistic and preclinical, so the proposed strategy to mitigate age-associated disease was not tested in humans.

Simplified

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.