Associated research paper (behind paywall):
A drug-like molecule engages nuclear hormone receptor DAF-12/FXR to regulate mitophagy and extend lifespan
Autophagy–lysosomal function is crucial for maintaining healthy lifespan and preventing age-related diseases. The transcription factor TFEB plays a key role in regulating this pathway. Decreased TFEB expression is associated with various age-related disorders, making it a promising therapeutic target. In this study, we screened a natural product library and discovered mitophagy-inducing coumarin (MIC), a benzocoumarin compound that enhances TFEB expression and lysosomal function. MIC robustly increases the lifespan of Caenorhabditis elegans in an HLH-30/TFEB-dependent and mitophagy-dependent manner involving DCT-1/BNIP3 while also preventing mitochondrial dysfunction in mammalian cells. Mechanistically, MIC acts by inhibiting ligand-induced activation of the nuclear hormone receptor DAF-12/FXR, which, in turn, induces mitophagy and extends lifespan. In conclusion, our study uncovers MIC as a promising drug-like molecule that enhances mitochondrial function and extends lifespan by targeting DAF-12/FXR. Furthermore, we discovered DAF-12/FXR as a previously unknown upstream regulator of HLH-30/TFEB and mitophagy.
I always thought the coumarin in cinnamon was a bad thing and the expensive stuff has less. In fact it’s hard to find here, so I kind of limit how much I use.
Now if the coumarin is a mitophagy agonist then will they change their story?
However, high levels of coumarin can cause liver damage. The general wisdom before this report was to limit coumarin exposure due to its toxicity.
Now the poison is the cure. Not sure what to believe at this point. You may not want to start dosing this until there’s more data available.
Yes - the study was in C. elegans (worms), so a long way from humans. And its more complex than just “coumarin”… its a benzocoumarin compound, so we really don’t know much about the molecule yet.