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Note that this is a preprint.
It has not yet been peer reviewed by a journal.
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AFAIK, good news for those of us fearing polypharmacological rejuvenescent interventions would always lead to mostly cancelling each others positive effects on aging. Should this study eventually prove exact, no need to mention the joy it will bring to the unchallenged emperor of the antiaging polypharmacology, Brian Johnson.
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Abstract
Analysis of lifespan‐extending compounds suggested the most effective geroprotectors target multiple biogenic amine receptors. To test this hypothesis, we used graph neural networks to predict such polypharmacological compounds and evaluated them in C. elegans. Over 70% of the selected compounds extended lifespan, with effect sizes in the top 5% compared to the DrugAge database. This reveals that rationally designing polypharmacological compounds enables the design of geroprotectors with exceptional efficacy.
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Key takeaways
- The most effective known geroprotectors act by polypharmacological mechanisms.
- Graph neural networks predicted polypharmacological geroprotectors with a hit rate of 70%.
- The predicted polypharmacological geroprotectors are exceptionally effective.
- The predicted polypharmacological mechanism was experimentally confirmed.
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Rationally designing polypharmacological compounds results in geroprotectors with exceptional efficacy.
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