We are all familiar with the term lifespan. However, someone with a long lifespan does not necessarily have a long healthy quality of life. A relatively new term gaining importance as we live longer is healthspan. Healthspan refers to the length of time a person is healthy, not just alive.
As we age, some people lose the ability to move, while others do not. Movement is an indicator of healthspan in both humans and worms. Researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) in Japan have conducted research in a bid to understand the genetic reasons some people have better mobility and subsequently, healthspans, compared to others.
More specifically, the researchers identified a gene known as C. elegans and looked at the role it plays in maintaining healthspan in roundworms as they age. C. elegans gene is also found in humans and has been identified as being useful for studying aging as it is easily manipulated in the lab and has a short lifespan. Their findings were recently published in G3: Genes, Genomes, Genetics.
Their research involved inserting random mutations of the C. elegans gene into worms. They then studied the offspring of the mutated worms to see which mutations affected the healthspan of the worms. Given that worms naturally head towards food, they measured the ability of the offspring to maintain their ability to move towards a food source as they age by placing them in the centre of a dish with food at the edge.
Any worms that failed to reach the food on their first day were characterized as having impaired movement at a young age and removed from the study. The researchers were only interested in how the mutations impacted movement with age.
The remaining worms were retested using the same method as they got older. The results showed that several worms had impaired movement as they aged. The DNA of these worms was sequenced and compared to that of a “normal” (or wild type) worms to uncover which mutations had occurred and help identify the genes responsible for the reduced ability to move.
This is how they identified a gene known as elpc-2 within C. elegans and the role it plays in healthspan. This gene is responsible for encoding part of the elongator complex. One of the many functions of the elongator complex is to assist with the correct folding of proteins and some of these proteins assist movement. In the mutant worms with damaged elpc-2 in C. elegans a working elongator complex was not observed, therefore explaining why the worm’s movement was impaired.
However, when these mutant worms were injected with a working copy of the elpc-2 gene, movement was restored. This confirms the role elpc-2 in C. elegans plays in movement and subsequently, healthspan. The researchers also inserted some worms with a fluorescent copy of the elongator complex, which showed that it is expressed throughout the body of the worm.
The findings also showed that several mutations impacted the healthspan but not the lifespan of the worm. This means some mutations did not affect how long a worm lived, only impacted how they moved. This observation indicates healthspan and lifespan do overlap, however, the genes responsible differ.
This research sheds light on the role genetics plays in healthspan. The study identified the gene elpc-2 in C. elegans plays an important role in maintaining movement and therefore healthspan in aging worms. The researchers intend on exploring other genes and their role in healthy aging and hope that once they have a more complete picture of the genes involved in healthy aging, they can then begin to manipulate these genes to improve healthspan. First in worms and then, hopefully in humans one day too.
Written by Lacey Hizartzidis, PhD
Kawamura K, Maruyama IN. Forward Genetic Screen for Caenorhabditis elegans Mutants with a Shortened Locomotor Healthspan. G3 (Bethesda). 2019 Jun 18. pii: g3.400241.2019. doi:10.1534/g3.119.400241.
New Gene Linked to Healthy Aging in Worms. EurekAlert website https://www.eurekalert.org/pub_releases/2019-07/oios-ngl071119.php. Accessed July 14, 2019.