Researchers discover gene related to healthy aging in worms

People with the same life span do not necessarily have the same quality of life. As we live longer, the extension of quality of life – "healthspan" – is gaining importance. Scientists from the Graduate University (OIST) of the Okinawa Institute of Science and Technology have discovered a gene related to healthy aging in the round worm C. elegans, highlighting the genetics of healthspan.

The team identified a gene called elpc-2 in C. elegans this plays an important role in maintaining health as the worm ages. This gene is conserved in humans – and worms with abnormalities in this gene have exhibited impaired mobility as they age. Older age movements are an indicator of health in humans and worms.

"As you get older, some people retain their full locomotor capacity, others do not, we want to understand the genetic reasons," says Dr. Kazuto Kawamura, first author of the study, published in G3: Genes, genomes, genetics. "This gene is one of many that plays a role in healthy aging.

"Our new experimental approach also allows us to simultaneously test hundreds of worms, which could be useful for other researchers."

C. "elegance"

C. elegans is a useful model for studying aging – it has a short shelf life and can be easily manipulated in the laboratory. Kawamura inserted random mutations into the genome of these worms. By studying the offspring of mutated worms, he was able to determine which mutations affected Healthspan. He measured whether organisms were able to maintain their ability to move to a food source as they age.

The worms were placed in the center of a dish with food at the edge. They go naturally to food, provided their movement is not impaired. All worms that did not reach food on the first day were deemed to have harmed the movement and were removed from the experiment. Kawamura was only interested in how this ability declined with age.

The remaining mutants were retested as they aged using the same approach, dubbed "edge badysis," as the worms migrated to the edge to reach the food. During these last tests, several worms with an alteration of the movements were identified.

These were then sequenced and their DNA compared to a normal wild-type worm to locate the mutations and identify the genes responsible.

"Creating hundreds of random mutants is not that difficult, but it's hard to determine which mutation is responsible for the impact on locomotory capacity."

Dr. Kazuto Kawamura

Understanding Healthspan

The researchers identified elpc-2 and its role in Healthspan. The gene encodes a portion of the elongator complex, which performs many important functions, including orchestrating the correct folding of proteins. Some of these proteins, in turn, may play a role in locomotion.

Mutants carrying the damaged elpc-2 gene did not have an active elongating complex, which explains why the movement was impaired. To confirm this, Kawamura injected these verses with a working copy of the gene and the movement was restored. He also created worms expressing a fluorescent copy of the elongator complex, illustrating its widespread expression throughout the body.

It is interesting to note that other genes have had a significant impact on healthspan – but not on lifespan. In other words, the underlying mutations do not affect much the life of a worm, but have an impact on the way they have moved. This demonstrates that, if health expectancies and lifespan overlap, the genetic basis is distinct.

The complex of elongators is only one part of the Healthspan puzzle. Kawamura then intends to explore other genes that play a role in healthy aging.

"Once we have a more complete picture of the genes involved, we can start manipulating them to improve health," says Kawamura. "First come C. elegans and maybe someday, humans. "