Testing the evidence that lifespan-extending compound interventions are conserved across laboratory animal model species

[RapAdmin]

A growing number of pharmaceutical and small molecule interventions are reported to extend the lifespan of laboratory animals including Caenorhabditis , Drosophila , and mouse. However, the degree to which these pro-longevity interventions are conserved across species is unclear. Here, we took two approaches to ask the question: to what extent do longevity intervention studies in Caenorhabditis and Drosophila recapitulate effects on mouse lifespan? The first approach analyzes all published reports on longevity in the literature collated by the DrugAge database, and the second approach focused on results designed for reproducibility as reported from the NIA-supported Interventions Testing Program (ITP) and the Caenorhabditis Interventions Testing Program (CITP). Using published data sources, we identify only modest sensitivity and specificity of Drosophila interventional studies for identifying pro-longevity compounds in mouse lifespan studies. Surprisingly, reported studies in C. elegans show little predictive value for identifying drugs that extend lifespan in mice. The results therefore suggest caution should be used when making assumptions about the translatability of lifespan-extending compounds across species, including human intervention.

Testing the evidence that lifespan-extending compound interventions are...

[adssx]

Sad but interesting.

@RapAdmin

Surprisingly, reported studies in C. elegans show little predictive value for identifying drugs that extend lifespan in mice.

Does this mean that there’s no relationship between the two models? (would be terrible) Or that compounds that succeed in C. elegans might not succeed in mice? (would be ok if mice are just more “selective”)

[DeStrider]

I think mice are more selective. That’s the opinion I’ve developed after listening to the Ora Bio folks and Dr. Kaeberlein.

Otherwise what’s the point of the million molecule challenge?

[John_Hemming]

I think the underlying issue is that unless we identify a mechanism or more then testing molecules is pot luck.

A worthwhile exercise, but not ideal.

[anon16510610]

MK response:

https://twitter.com/mkaeberlein/status/1617749253887262721

[RapAdmin]