Study identifies mitochondrial circular RNAs in aging and senescence

A new research paper was published in Volume 18 of Aging-US on February 10, 2026, titled "Aging-associated mitochondrial circular RNAs."

Led by first author Hyejin Mun from the University of Oklahoma - with corresponding authors Je-Hyun Yoon from the University of Oklahoma and Young-Kook Kim from Chonnam National University Medical School - the study profiles mitochondrial circular RNAs in Peripheral Blood Mononuclear Cells (PBMCs) from young and old human cohorts and probes how mitochondrial circRNAs and the mitochondrial RNA-binding protein GRSF1 relate to mitochondrial metabolism and cellular senescence.

Using total RNA sequencing of PBMCs from young and old donors and complementary cell-based experiments, the authors report that a large fraction of circular RNA junctions originates from the mitochondrial genome, with MT-RNR2 producing the most abundant circular junctions. They show that circMT-RNR2 levels are depleted in older cohorts and in replicative senescence of human fibroblasts, and that the mitochondria-localized RNA-binding protein GRSF1 interacts with both linear and circular MT-RNR2. Loss of GRSF1 reduced circMT-RNR2 levels, decreased mitochondrial TCA intermediates (fumarate and succinate), and accelerated cellular senescence and mitochondrial dysfunction - findings that link mitochondrial circRNAs to mitochondrial energetics and proliferative status in younger cells. 

"Taken together, our findings demonstrate the existence and possible function of circular MT-RNR2 during human aging and senescence, implicating its role in promoting the TCA cycle."

The authors note key limitations and outline next steps: clarifying the biogenesis mechanism of mitochondrial circular RNAs (including whether trans-splicing contributes), mapping direct interactions between mitochondrial transcripts and metabolic enzymes, and performing mechanistic studies (in vivo and in additional human cohorts) to test how circMT-RNR2 and GRSF1 influence mitochondrial energetics and organismal aging. These follow-ups will determine whether mitochondrial circular RNAs are actionable targets for modulating mitochondrial metabolism or delaying aspects of cellular aging.