Aging-linked Mitochondrial Circular RNAs Discovered

New research profiles mitochondrial circular RNAs and links them to mitochondrial metabolism and cellular senescence.

Published on Feb. 25, 2026

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Researchers have published a new study in the journal Aging-US that profiles mitochondrial circular RNAs in young and old human cohorts. The study found that a large fraction of circular RNA junctions originate from the mitochondrial genome, with the MT-RNR2 gene producing the most abundant circular junctions. Levels of the circMT-RNR2 transcript were depleted in older individuals and in replicative senescence of human fibroblasts. The mitochondria-localized RNA-binding protein GRSF1 was shown to interact with both linear and circular MT-RNR2, and loss of GRSF1 reduced circMT-RNR2 levels, decreased mitochondrial TCA intermediates, and accelerated cellular senescence and mitochondrial dysfunction.

Why it matters

This research provides new insights into the role of mitochondrial circular RNAs and their potential links to mitochondrial energetics and cellular aging processes. Understanding the biogenesis and functions of these mitochondrial circular RNAs could lead to new strategies for modulating mitochondrial metabolism and delaying aspects of cellular senescence.

The details

The study, led by researchers from the University of Oklahoma and Chonnam National University Medical School, used total RNA sequencing of peripheral blood mononuclear cells (PBMCs) from young and old donors, as well as complementary cell-based experiments, to profile mitochondrial circular RNAs. They found that a large fraction of circular RNA junctions originate from the mitochondrial genome, with the MT-RNR2 gene producing the most abundant circular junctions. Levels of the circMT-RNR2 transcript were depleted in older cohorts and in replicative senescence of human fibroblasts. The researchers also showed that the mitochondria-localized RNA-binding protein GRSF1 interacts with both linear and circular MT-RNR2, and that loss of GRSF1 reduced circMT-RNR2 levels, decreased mitochondrial TCA intermediates (fumarate and succinate), and accelerated cellular senescence and mitochondrial dysfunction.

  • The study was published on February 10, 2026 in the journal Aging-US.
  • The research was conducted using peripheral blood mononuclear cells (PBMCs) from young and old human cohorts.

The players

Hyejin Mun

First author of the study from the University of Oklahoma.

Je-Hyun Yoon

Corresponding author of the study from the University of Oklahoma.

Young-Kook Kim

Corresponding author of the study from Chonnam National University Medical School.

GRSF1

A mitochondria-localized RNA-binding protein that interacts with both linear and circular MT-RNR2 transcripts.

MT-RNR2

A gene in the mitochondrial genome that produces the most abundant circular RNA junctions.

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What they’re saying

“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 (Aging-US)

What’s next

The authors note key limitations and outline next steps, including clarifying the biogenesis mechanism of mitochondrial circular RNAs, 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.

The takeaway

This research provides new insights into the role of mitochondrial circular RNAs and their potential links to mitochondrial energetics and cellular aging processes. Understanding these mitochondrial circular RNAs could lead to new strategies for modulating mitochondrial metabolism and delaying aspects of cellular senescence.