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Rodent safety archives flag compounds linked to better survival

In rodent pesticide studies, 27 of 154 substances were linked to survival increases of at least 10% at study termination.

Paper by Satomi Miwa, Olena Kucheryavenko, Kristin Herrmann, 6 more authorsThomas von Zglinicki · Faculty of Medical Sciences Newcastle University Newcastle upon Tyne UK
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Graphical abstract. Miwa et al., CC BY
Study of pesticide-exposed rodentsInterventions

Limit: Survival at study termination, rather than total lifespan, drove candidate selection

Edited by Boris Djordjevic · AgingResearch.News

Paper
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Researchers analyzed long-term pesticide safety experiments in rodents, with at least 50 animals per dose and sex. They searched a random subset of the German Federal Institute for Risk Assessment’s electronic archive. Studies covering 154 substances met their criteria; 27 substances were linked to increased survival at study termination.

The team examined 15 substances whose identities could be disclosed publicly. In mammalian cells grown in the lab, roughly half altered oxygen consumption by mitochondria, the structures that produce usable energy. Bromoxynil acted as a mitochondrial uncoupler, separating fuel use from energy production. In separate experiments in Caenorhabditis elegans worms, bromoxynil improved several measures of healthy lifespan without compromising overall health.

Why it matters

Mild stress can trigger adaptive responses that improve resilience, a rationale for testing compounds in healthy-aging research. The authors propose using toxicity archives to help select candidates for further experiments in mammals.

Caveats

The archive analysis identified candidates based on survival at study termination; the authors call for rigorous preclinical follow-up. The findings do not establish safety or benefits in people.

Where the evidence stands

Oxidative phosphorylation

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.

  • 304 independent labs in 48 countries
  • 45 findings against
  • Funders: National Institutes of Health and others
  • 66 of 619 findings with company ties

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