Gene Linked To Healthy Aging In Worms Identified

The gene elpc-2 has been identified as playing an important role in maintaining healthspan as the worm ages; this gene is conserved in humans, and worms with defects in this gene display impaired movement with age. Changes in movement with age is an indicator of healthspan in humans and C. elegans. 

“As we age, some people keep full locomotor ability while others do not, and 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 among many playing a role in healthy ageing. Our new experimental approach also allows us to test hundreds of worms simultaneously, which could be useful for other researchers.”

These worms make useful study models due to their short lifespan and that they can be easily manipulated in laboratories. Random mutations were inserted into C. elegan genomes, by studying the offspring of the mutated worms allowed the researchers to test which mutation affected healthspan such as whether they were able to maintain their ability to move towards food sources as they aged. 

When worms as placed in a dish with food they will naturally head towards the food proving their movement is not impaired; any that fail to reach the food on the first day were deemed to have impaired movement at a young age and were removed from the experiment as the team was only investigating how their ability declined with age. 

The remaining mutant worms were tested as they aged using the same approach, several worms were identified showing impaired movement. The identified worms were then sequenced and their DNA was compared with normal wild type worms to investigate the mutations and locate the genes responsible. 

“Creating hundreds of random mutants is not so difficult,” says Kawamura, “but it is difficult to figure out which mutation is responsible for the impact on locomotor ability.”

Elpc-2 was identified and its role in healthspan; it encodes part of the elongator complex which has many functions including orchestrating correct folding patterns, and some of these proteins in turn may have roles in locomotion. 

Worms were found to be lacking a working elongator complex that had damaged elpc-2 genes, which may explain why movement was impaired; to confirm this these worms were injected with working copies of the gene and movement was observed to be restored, and worms expressing a fluorescent copy of the elongator complex were also created to illustrate its widespread expression throughout the worm’s body. 

Additional genes were identified that had strong impacts on healthspan but not lifespan, meaning the underlying mutations didn’t affect how long a worm lived but it did impact how they moved. Findings demonstrate that healthspan and lifespan do overlap but the genetic basis is distinct. 

According to Kawamura the elongator complex is just one section of the healthspan puzzle, next the Okinawa Institute of Science and Technology Graduate University scientists have plans to investigate other genes that play roles in healthy aging. 

“Once we have a more complete picture of the genes involved, we can begin to manipulate them to improve healthspan,” says Kawamura. “First in C. elegans and perhaps, one day, humans.”