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Renal Failure

Gut microbe-derived compound promotes kidney aging in mice

Reducing a circular RNA weakened the compound’s effects in male mice given it in drinking water for 16 weeks.

Paper by Lu Zeng, Limin Wei, Shanshan Liang, +2 more authorsFanfan Gao · The First Affiliated Hospital of Xi’an Jiaotong University

Our read

Mechanisms
Studied:
Experiments in male C57BL/6J mice, 16 weeks, against control mice (Randomized)
What changed:
Kidney aging markers were higher in TMAO-treated mice than in control mice
The catch:
Only 4 mice per group contributed to the kidney senescence analyses

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
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Male C57BL/6J mice purchased at eight weeks old were randomly assigned to groups of six in an animal experiment. They received trimethylamine N-oxide, a gut microbe-derived compound, in drinking water at 1.5% for 16 weeks. Compared with controls, their kidneys showed more signs of senescence, a state in which cells stop dividing.

The compound also increased circVmn2r1, a ring-shaped RNA molecule, and activated an inflammation-triggering protein complex. Reducing this RNA with gene-silencing injections twice weekly for four weeks weakened the increases in senescence and inflammation markers in mouse kidneys. Mouse kidney tube-lining cells grown in the lab also showed senescence after exposure to the compound at 100 millimolar for 72 hours. Reducing the same RNA partly weakened these effects.

Why it matters

For kidney aging under metabolic stress, the authors identified circVmn2r1 as a potential therapeutic target.

Caveats

The kidney-aging findings relied on molecular markers and staining in one male mouse strain and mouse cells grown in the lab. Although six mice were assigned per group, reported kidney analyses used three or four per group.

Where the evidence stands

CIRCVMN2R1

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

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

  • 2 independent labs in 1 country
  • Funders: Key Research and Development Projects of Shaanxi Province and 1 more

Inflammation

Cells, worms or flies, mice and humans: replicated by independent labs.

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.

  • 1,044 independent labs in 77 countries
  • 204 findings against
  • Funders: National Natural Science Foundation of China and others
  • 382 of 4,593 findings with company ties

From the paper

Limitation

First, while we establish TMAO as an inducer of circVmn2r1, the precise transcriptional or post-transcriptional mechanism by which it upregulates this circRNA requires further investigation.

Discussion

Quoted word for word from the full text on tandfonline.com.

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