Mining a random subset of the German BfR archive of regulatory long-term rodent pesticide toxicity studies identified 27 of 154 substances (18%) that significantly increased survival, about half of the 15 disclosable substances perturbed mitochondrial oxygen consumption, and bromoxynil acted as a mitochondrial uncoupler that improved healthspan indicators in C. elegans.
Key Findings
Results
Regulatory rodent toxicology archives contained a substantial fraction of substances associated with increased survival at study termination.
The authors mined a random subset of the German Federal Institute for Risk Assessment (BfR) electronic archive for long-term rodent pesticide studies with ≥50 animals per dose and sex.
From qualifying studies covering 154 substances, 27 substances (18% of entries) significantly increased survival at study termination (≥10% increase, p<0.05).
The approach uses existing mandated regulatory data, consistent with 3Rs principles.
Results
Roughly half of the 15 publicly disclosable survival-increasing substances perturbed mitochondrial oxygen consumption in mammalian cells.
Fifteen of the 27 substances could be publicly disclosed and were examined further.
Mitochondrial oxygen consumption rates were measured in mammalian cells.
This suggests mitochondrial mechanisms may be emergent among the survival-extending compounds.
Results
Bromoxynil was identified as a mitochondrial uncoupler.
Bromoxynil was among the substances that increased survival in rodent regulatory studies.
Its effects on mammalian cell oxygen consumption were consistent with mitochondrial uncoupling.
Results
Bromoxynil improved multiple healthspan indicators in C. elegans without compromising organismal health.
Back-translation to Caenorhabditis elegans was used to test bromoxynil.
Multiple healthspan indicators were improved.
No compromise of organismal health was reported.
Conclusions
Regulatory toxicity archives can be repurposed to identify candidate compounds, targets and mechanisms for healthy ageing research.
Such archives generate lifespan and chronic toxicity data from large cohorts across multiple dose groups, which suits detection of hormetic dose-response effects.
The authors propose this approach complements conventional screening pipelines.
They suggest the datasets could support AI-driven prioritisation of interventions for rigorous preclinical follow-up.
What This Means
Testing whether a compound extends lifespan in mammals is slow and expensive. This study took a different route: it looked through existing safety records that companies must submit to regulators when seeking approval for pesticides. These long-term rodent studies use many animals and several doses, and record survival. The researchers examined a random subset from the German Federal Institute for Risk Assessment covering 154 substances and found that 27 (18%) were linked to significantly better survival at the end of the study.
For the 15 substances that could be publicly named, about half altered how mitochondria, the cell's energy producers, use oxygen in mammalian cells. One compound, bromoxynil, acted as a mitochondrial uncoupler, meaning it makes mitochondria work in a slightly less efficient, mildly stressful way. In the roundworm C. elegans, bromoxynil improved several measures of healthy ageing without apparent harm to the animals.
This research suggests that existing regulatory safety data may be a useful, low-cost source of leads for ageing research and fits with efforts to reduce animal use by reusing data. The findings do not show that these pesticides are safe or beneficial for people. The survival signals come from toxicology studies, and the candidates would need careful, controlled follow-up before any conclusions about healthy ageing could be drawn.