AgingThat Worm Looks Fantastic for its Age!
C. elegans ages like humans and other organisms, i.e., it exhibits changes in its appearance and behavior as it gets older. As worms age, they start to become less transparent and to move more slowly. Since C. elegans grows old and dies in about three weeks, scientists use it as a model to study aging and lifespan by determining if mutant worms age more slowly and live longer compared to normal worms.
Scientists working with worms have identified several genes involved in aging, including a gene called daf-2. C. elegans that have mutations in the daf-2 gene and produce a low amount of DAF-2 protein live 30-50% longer than normal and act like younger worms despite being quite old (for a worm!). It is like seeing a centenarian looking and acting like a teenager. Since reducing the amount of the DAF-2 protein results in a longer lifespan, it seems that the normal function of the DAF-2 protein produces shorter lifespan for C. elegans.
The graph in Figure 1, at the left, shows the lifespan of worms that have a reduced level of DAF2 protein. In the experiment, scientists tested multiple worms of four different types: normal worms (black line), worms with a reduced amount of DAF2 protein due to a mutation called e1368 (blue line), worms with almost no DAF-2 function, from a combination of thee1368 mutation and RNAi treatment (as described the Vignette on RNA interference), and worms with almost no DAF2 protein function and no reproductive organs (red line). The x-axis shows the number of days that the worms were observed. The y-axis shows the fraction of worms still alive on each day examined. These results indicate that worms with a lowest level of DAF-2 protein live longer, especially if the reproductive organs have also been removed.
The normal function of the daf-2 gene is to control several other genes and allow tissues to respond to hormones that affect lifespan. After the work in C. elegans identified the daf-2 gene as important for aging, subsequent studies have suggested that other animals have genes related to daf-2 that might be important for longevity. The role daf-2 related genes might play in aging in humans is being investigated.
Click on the image to the right to check out a quick movie of two active, 144-day-old worms with low DAF-2 levels and no reproductive organs. Remember -- C. elegans normally die in under 21 days! The movie appears on the Kenyon Lab Web site, University of California, San Francisco -- which also offers more information about using worms to study aging.