Given the chance, there are very few of us who wouldn't want to slow down the aging process. Chasing that fountain of youth is a major branch of medical science at the moment, and a hardy little worm known as C. elegans is probably the most prolific test subject. Now, a team at Scripps Research has found that blocking a particular enzyme can extend the lifespan of these worms by almost half again.
C. elegans has a similar genome to humans and shows clear signs of aging during its short, two- or three-week-long lifespan, making it an almost-perfect model for aging studies. In the past, these little worms have been used to investigate how the brain-gut connection forms a kind of "axis of aging," the genetics behind why we haven't evolved immortality, and watch how certain drug cocktails affect the aging process.
In the new study, the team examined the roles of a long list of enzymes, looking for ones that might play a part in aging. By disrupting these enzymes in worms, they could see what effect it had on the animals' lifespan, which might reveal some new targets for future anti-aging research. To do so, the team ran through a series of about 100 small-molecule compounds that blocked enzymes called serine hydrolases.
"Metabolic processes are very important in determining the rate of aging and lifespan, and serine hydrolases are major metabolic enzymes, so we thought there was a good chance we'd find an important aging-related enzyme this way," says Alice Chen, first author of the study.
The team tested these compounds on worms that were one day into their adulthood, then measured their lifespans. Several compounds were found to extend the worms' longevity by more than 15 percent over the average. But one in particular stood out: a carbamate compound called JZL184 boosted the worms' average lifespans by an astonishing 45 percent. At the age of 30 days, more than half of these worms were still alive and healthy, while almost all of the control worms had died.
In a strange twist, the researchers initially weren't sure why JZL184 worked at all. This compound was designed for use in mammals, and worms lack the enzyme it inhibits, known as MAGL. On closer inspection, the team found that it instead works on a different pathway that performs the same function that MAGL does in mammals.
The team says that by making the connection between these two pathways in the different species, we now know where to focus future work on worms, which might reveal new anti-aging possibilities in humans.
The research was published in the journal Nature Chemical Biology.
Source: Scripps Research
