The nematode C Elegans is extensively used for the study of lifespan regulation. The simple 2000 cell organism only lives for 15 days so interventions which may prolong survival are quick and easy to measure. Furthermore, the genome and metabolic pathways of the organism are well understood.
It is known that worms can be induced to live more than double their lifespan by exposing them to environmental stresses such as starvation. In response to those stresses the worms enter a near suspended animation state called dauer.
The molecular pathways leading to dauer formation are understood and mainly involve a gene called DAF-9. When DAF-9 expression or function is reduced, the worms live longer. In studies the ability to induce reduce DAF-9 expression has heretofore been carried out by modifying the worms’ genome; no drugs have existed which can manipulate the pathway.
In the current study, scientists report the discovery of a new compound they call dafadine-A which directly inhibits DAF-9.
The small molecule compound was discovered using a screening assay of thousands of molecules looking for any that could induce dauer.
In the study the researchers carefully proved the compound acts directly on the DAF-9 pathway and that dauer formation was not due to some secondary factors. Finally they grew worms in a dafadine-A containing medium and demonstrated lifespan was extended by 29%.
Particularly exciting the researchers also showed that the novel compound also acts on the analogous mammalian pathway suggesting it is possible the compound could extend lifespan of mammals.
Whether it is safe and effective in humans is of course unknown, and it may be a long way to finding out.
