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bioRxiv

Age-linked RNA shifts in mice mostly point to gene regulation

Across mouse tissues, 36.5–42.6% of switches altered the predicted protein-coding sequence, while 11–18% involved RNA versions encoding an identical protein.

Paper by N. Paidimukkala, S. S. Ali, L. Laux, +6 more authorsJ. Wang · University of Minnesota
RNA strands with looped folds and differing tail lengths sit beside a brain section, round fat cells, a lobed liver, and a laboratory mouse.

Our read

AI & data
Studied:
Preprint: experiments in naturally aging mice and Ercc1 knockout mice
What changed:
Across mouse tissues, 36.5-42.6% of age-linked RNA switches altered the predicted protein-coding sequence
The catch:
RNA features and computer predictions do not directly measure effects on tissue function
In the record:
One of 25 papers on IGHM on record: none yet with results in people, 3 in animals.

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
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Mouse brain, liver and fat tissue were examined in an animal study of age-associated changes in RNA, the molecules made when genes are read. The researchers analyzed shifts in the use of different RNA versions produced from the same gene during natural aging and in mice with a gene disabled.

Across tissues, 36.5–42.6% of switches altered the predicted protein-coding sequence. Noncoding alternatives were involved in 31.2–36.5%, while 11–18% involved versions encoding an identical protein. RNA tended toward longer noncoding tail regions in the brain and shorter ones in fat tissue. The authors interpreted the switches as predominantly regulatory, with consequences for protein structure restricted to tissue-specific events.

Why it matters

Age-linked changes in how cells process RNA may offer biomarkers of aging.

Caveats

RNA features and computer predictions cannot by themselves establish how the switches affected tissue function. The findings are from mice, and the preprint has not been peer-reviewed.

Where the evidence stands

ERCC1

Mice: replicated by independent labs. Cells and humans: a single group. Worms or flies: nothing yet.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 12 independent labs in 7 countries
  • 5 findings against
  • Funders: National Institute on Aging and others
  • 5 of 47 findings with company ties

RNA splicing

Cells and mice: replicated by independent labs. Worms or flies and humans: a single group.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 43 independent labs in 13 countries
  • 1 finding against
  • Funders: National Institutes of Health and others
  • 3 of 54 findings with company ties

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The paper

A multi- tissue atlas of age-associated differential transcript usage in mouse reveals predominantly regulatory isoform switching across brain, liver, and adipose

N. Paidimukkala, S. S. Ali, L. Laux, +6 more authorsJ. Wang

University of Minnesota

bioRxiv, Nov 11, 2026, Open access, Preprint, not yet peer-reviewed

doi.org/10.64898/2026.11.10.765779

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