Altering protein in C. elegans offers hope for anti-ageing drugs

Researchers have been able to manipulate the lifespans of C. elegans by altering the VRK-1 protein, offering a potential target hope for anti-ageing drugs.

C. elegans - protein for anti-ageing

By altering the activity of proteins found in roundworm cells, researchers have been able to dial up and down the creatures’ lifespans. They controlled the roundworm proteins that tell them to convert sugar into energy when their cellular energy is running low. According to the researchers, humans also have these proteins, offering the potential to develop anti-ageing drugs. 

From the Korea Advanced Institute of Science and Technology (KAIST), the researchers used the roundworm Caenorhabditis elegans (C. elegans), a millimeter-long nematode commonly used in lab testing. 

The team report that the proteins VRK-1 and AMPK work in tandem in roundworm cells, with the former telling the latter to get to work by sticking a phosphate molecule, composed of one phosphorus and four oxygen atoms, on it. In turn, AMPK’s role is to monitor energy levels in cells, when cellular energy is running low. In essence, VRK-1 regulates AMPK, and AMPK regulates the cellular energy status.

Using a range of different biological research tools, including introducing foreign genes into the worm, the researchers were able to dial up and down the activity of the gene that tells cells to produce the VRK-1 protein. 

They confirmed that the overexpression, or increased production, of the VRK-1 protein boosted the lifespan of the C. elegans, which normally lives just two to three weeks and the inhibition of VRK-1 production reduced its lifespan.

The research team found that the activity of the VRK-1-to-AMPK cellular-energy monitoring process is increased in low cellular energy status by reduced mitochondrial respiration, the set of metabolic chemical reactions that make use of the oxygen the worm breathes to convert macronutrients from food into energy.

Figure 1

VRK-1 that was visualised by tagging with green fluorescence protein (GFP) in C. elegans [credit: Seung-Jae V LEE, KAIST].

It is known that mitochondria, the energy-producing engine rooms in cells, play a crucial role in ageing and declines in the functioning of mitochondria are associated with age-related diseases, the researchers say. At the same time, the mild inhibition of mitochondrial respiration has been shown to promote longevity in a range of species, including flies and mammals.

When the team performed similar experiments with cultured human cells, they found they could also replicate this ramping up and down of the VRK-1-to-AMPK process that occurs in roundworms.

“This raises the intriguing possibility that VRK-1 also functions as a factor in governing human longevity and so perhaps we can start developing longevity-promoting drugs that alter the activity of VRK-1,” explained lead researcher Professor Seung-Jae V Lee.

The group say at the very least, the research points in an interesting direction for investigating new therapeutic strategies to combat metabolic disorders by targeting the modulation of VRK-1. Metabolic disorders involve the disruption of chemical reactions in the body, including diseases of the mitochondria.

These findings were published in Science Advances.