Worms in space: Spaceflight slows aging of the model organism C. elegans

I study genetics of aging in the nematode worm Caenorhabditis elegans. C. elegans is a simple animal model organism that has been studied in the lab for a few decades. The adult roundworm is about 1mm long and consists of about 1000 cells. Conveniently, the fate of every cell division from fertilization until the worm reaches adulthood (which takes about 3 days) has been mapped out by scientists, so that we know exactly how every cell division occurs in order for the worm to develop into an organism of multiple tissues and specialized cell types. Additionally, scientists have also sequenced the entire C. elegans genome, so we can study any gene with any particular function of interest. These two key features, along with many other lab techniques that have been well-established when studying worms, make C. elegans an attractive animal model system. Scientists may utilize C. elegans to study neurobiology, development, stem cell biology, etc. I utilize C. elegans as a model for studying aging because many genes important for regulating aging process (such as genes in hormonal pathways, genes involved in nutrient uptake, and genes expressed in the mitochondria) are conserved from C. elegans to humans. Additionally, C. elegans adult worms only live for 2-3 weeks, so I can easily conduct multiple experiments over the entire lifespan of a worm in a short amount of time.
              While perusing through recent scientific articles about C. elegans aging, I came across an article by Yoko Honda and colleagues, entitled “Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans” (Scientific Reports 2: 487, 2012). Here is the article link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390002/pdf/srep00487.pdf. The title immediately caught my attention, not just because I am interested in genes that regulate longevity in C. elegans, but mostly because these scientists studied longevity of C. elegans in space! Their research is literally out of this world! (Sorry for the cheesy pun.)  Oftentimes a space exploration will also carry some lab specimens along for the ride, so that we can learn more about how spaceflight impacts living things. Honda and colleagues claim that studying the impact of spaceflight on C. elegans aging is important because soon humans will be spending more time in space as we explore other planets or colonize the moon. These statements are a bit far-fetched because our daily lives will not resemble an episode of “Futurama” any time soon; however, we can argue that studying the effect of spaceflight on aging is intriguing from a physics standpoint; remember learning about Albert Einstein’s theory that if you travel into space and come back to Earth, you will be much younger than you were supposed to be? This is part of the theory of relativity: the faster you travel through space, the slower you will travel through time.

             By using C. elegans as a model system, Honda and colleagues have shown that this is actually true – worms do slow down the natural process of aging when they are in space! The researchers were able to make this claim based on a few findings from their research. They utilized data from the International C. elegans Experiment First Project, in which they compared data from “space-flown” vs. “ground control worms” over a 16-day period, where the worms were either on ground for 16 days or were or ground for 5 days and then space-flown for 11 days.

In the first experiment, the scientists looked at the accumulation of protein aggregates consisting of 35-glutamine repeats. It was previously shown that these aggregates accumulate with increasing age in the worm; in fact, these are the same type of aggregates that accumulate in the brain of patients with polyglutamine diseases like Huntington’s Disease. The researchers tagged these aggregates with a fluorescent protein in order to easily count the number of aggregates under the microscope by looking at the amount of fluorescence. They saw that spaceflight reduced the accumulation of these polyglutamine aggregates, in which worms of the same age that were space-flown had fewer aggregates than worms that were not space-flown. As accumulation of these aggregates is a biomarker for aging, this means that the space-flown worms were aging more slowly!

           The second experiment which showed that spaceflight slows down worm aging was conducted by using a DNA microarray, which is a technique to measure changes in gene expression between two different conditions. (This is where the sequenced genome of C. elegans comes in handy because the DNA microarray allows you to look at many, many genes at once.) For this experiment, scientists compared gene expression between space-flown vs. ground control worms. There were many genes that were either up- or down-regulated compared between the two different environmental conditions. However, Honda and colleagues analyzed this data and noticed that seven genes important for neuronal and endocrine signaling were down-regulated in the space-flown worms compared to the ground control worms. By applying certain lab techniques to worms that were not space-flown, the researchers saw that inactivation of these same seven genes resulted in increased longevity of the worms. Therefore, when these genes are not functioning, the worms live longer, which means that these genes antagonize longevity. Since the space-flown worms had much lower expression levels of these genes, this indicates that the space-flown worms were aging more slowly than their ground control counterparts. The researchers went on to demonstrate that, for three of these seven genes, there is less accumulation of polyglutamine aggregates when the genes are inactivated, further indicating that these genes antagonize longevity when functioning normally.

Honda and colleagues concluded from these experiments that C. elegans worms age more slowly due to a neuronal and endocrine response to cues from their space-flight environment, as compared to worms that are aging and are not space-flown. By utilizing this model organism, the researchers demonstrated through a few experiments that biological aging is, in fact, affected by space flight, just as Albert Einstein had predicted.