image: Figure 2. MT-RNR2 produces circular RNAs depleted in PBMCs of old cohort and in human diploid fibroblasts, WI-38. (A) Start and end of circMT-RNR2 from linear MT-RNR2. Position of primers to detect circular and linear MT-RNR2 are presented. (B) Circular RNA junctions identified from previous study (Jeck et al., 2013). (C) Abundance of circMT-RNR2 junction analyzed from total RNA-seq of PBMCs from young and old cohorts. (y-axis: count of circMT-RNR2 junction) (D) RT-qPCR analysis of circMT-RNR2 and western blot analysis of GRSF1 and HSP90 in WI-38 human diploid fibroblasts at different population doubling level (PDL).
Credit: Copyright: © 2026 Mun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“Here, we report profiles of circular RNAs annotated to mitochondrial chromosome, chrM, in young and old cohorts.”
BUFFALO, NY — February 24, 2026 — 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.
Paper DOI: https://doi.org/10.18632/aging.206354
Corresponding authors: Je-Hyun Yoon – jehyun-yoon@ou.edu
Young-Kook Kim – ykk@jnu.ac.kr
Abstract video: https://www.youtube.com/watch?v=f8uZ6_tcOHw
Keywords: circular RNA, MT-RNR2, GRSF1, TCA cycle, aging
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Journal
Aging-US
Method of Research
News article
Subject of Research
Not applicable
Article Title
Aging-associated mitochondrial circular RNAs
Article Publication Date
10-Feb-2026
COI Statement
The authors declare no conflicts of interest related to this study.