EDITOR'S CHOICE IN METABOLIC SCIENCE
R. Xiao et al., “A genetic program promotes C. elegans longevity at cold temperatures via a thermosensitive TRP channel,” Cell, 152:806-17, 2013.
Many animals live longer at cold temperatures. The dominant explanation has been that low temperatures simply slow down all chemical reactions, including the ones that lead to aging. “People assume that it’s just a passive process,” says Shawn Xu, a neurobiologist and geneticist at the University of Michigan. But he and colleagues have found that in C. elegans, the cold-sensitive ion channel TRP is involved in actively promoting longevity when the temperature drops.
For years, Xu had been studying how TRP channels, encoded by the TRPA-1 gene, influence neuronal signaling and behavior. His team found that C. elegans engineered to lack TRPA-1 had shorter life spans at low temperatures than worms without the mutation, whereas worms producing higher levels of TRPA-1 lived longer at low temperatures. Both mutants lived a normal life span at normal temperatures.
The TRP channel activates an anti-aging pathway by letting calcium ions into the cell, Xu and his team found. The calcium signaling sets off a cascade of kinases, which activate the transcription factor DAF-16, famous for its involvement in anti-aging pathways.
Xu and colleagues engineered worms to express human TRP channels instead of their own and found that the worms still had enhanced longevity at low temperatures. The horseradish-like condiment wasabi also activates human TRP channels, and Xu was able to promote longevity even at normal temperatures by giving the transgenic worms wasabi’s active ingredient. “It’s a very exciting finding from a basic-science point of view, and possibly from an application point of view,” says Bruno Conti, a chemical physiologist at The Scripps Research Institute in California.