Sci. Aging Knowl. Environ., 7 January 2004
Worms live longer after losing neurons for smell and taste
Unlike guys, nematodes gain from being insensitive: Mutations that deaden their senses also prolong their survival. New work identifies the neurons that underlie this life-extending effect, supporting the idea that worms alter their life span based on perceptions of their surroundings.
Four years ago, molecular geneticist Cynthia Kenyon of the University of California, San Francisco, and graduate student Javier Apfeld discovered that mutations that hamstring nematodes' sensory neurons--which detect odors, tastes, and temperature--can stretch life span by up to 100%. Their work also suggested that sensory cells exert their influence through the insulin/insulin-like growth factor-1 (IGF-1) pathway, which researchers can manipulate to extend longevity (see "One for All"). For instance, worms with a faulty version of a protein called DAF-2, which performs a key step in the insulin/IGF-1 pathway, survive more than twice as long as normal. If the sensory cells also act in that pathway, but upstream of daf-2, disabling the cells wouldn't extend life in worms with defective daf-2--which is exactly what the team found. However, the perception-dulling mutations blank out all the worm's sensory neurons.
To find out which cells shape life span, Kenyon and postdoc Joy Alcedo used a laser to remove combinations of smell and taste neurons in developing worms, then measured the longevity of the adults. Eliminating either of two taste neurons added time to the worms' lives, but knocking out a third taste neuron as well cancelled that life-span increase. The result indicates that some of these neurons normally promote survival and others trim it, the scientists conclude. Zapping a smell neuron or a combination of two of these cells also boosted longevity. The researchers then obliterated neurons in worms lacking daf-16, a gene that is necessary for life extension through the insulin/IGF-1 pathway. Knocking out taste cells didn't prolong life in these worms, but blasting the smell neurons did. That distinction suggests that the taste neurons prod the insulin/IGF-1 pathway, whereas the olfactory neurons act through a different one. The results reveal that certain sensory cells monitor the worm's environment and lengthen or shorten its life span accordingly, Kenyon says. However, nobody yet knows which environmental chemicals the worms respond to. Last year, Kenyon and colleagues reported that contrary to the results of prior studies, the insulin/IGF-1 pathway's activity in the worm's gut has a bigger impact on longevity than does its activity in neurons (see "Visceral Reaction"). She says that the new results don't conflict with the previous finding, which analyzed molecular events farther along in the pathways that govern life span.
Sensory neurons pump out insulin-like proteins. Now, researchers should focus on determining which environmental cues influence production of these messengers and whether the chemicals alter life span, says geneticist Cathy Wolkow of the National Institute on Aging in Baltimore, Maryland. Another mystery is whether sensory neurons adjust longevity in other organisms, including mammals. In people, Kenyon notes, the aroma of food spurs the pancreas to spill insulin into the blood, indicating a link between the sense of smell and a hormone that might be involved in human longevity. But only further work will reveal whether we too have a nose for longer life.
January 7, 2004
Science of Aging Knowledge Environment. ISSN 1539-6150