The work was done in an animal species widely used as a model for genetic and biological research, but the finding has broader applications for research into the genetics of ageing.
Corresponding author of a paper on the work, Adriana San Miguel, is also an assistant professor of chemical and biomolecular engineering at NC State.
She said: “There are a lot of genes out there that we still don’t know what they do, particularly in regard to ageing.
“That’s because this field faces a very specific technical challenge: by the time you know whether an organism is going to live for a long time, it’s old and no longer able to reproduce.
“But the techniques we use to study genes require us to work with animals that are capable of reproducing, so we can study the role of specific genes in subsequent generations.
“To expedite research in this field, we wanted to find a way of identifying genes that may be relevant to ageing while the organisms are still young enough to work with.”
For this work, the researchers focused on a species of roundworm called C. elegans, which is one of the most important model species for research into genetics and ageing.
Specifically, the researchers focused on protein aggregation in cells, which is well established as being related to ageing.
Here’s how the new method for identifying genes that may be relevant to ageing works.
First, the researchers expose thousands of C. elegans to a chemical that induces random genetic mutations.
The researchers then use an autonomous, high-throughput system that allows them to identify which roundworms have high levels of protein aggregation in their cells without harming them, but while they’re still young enough to reproduce.
The roundworms that have higher levels of protein aggregation, which are expected to live for a shorter period of time, are then separated from the others using an automated, microfluidic system and observed to see how long they live.
Once the roundworms die, researchers have established protein aggregation and lifespan data for each of the roundworms.
The roundworms with the highest protein aggregation and the shortest lifespans can be prioritised for study, since there is an increased likelihood that their mutations affected their ageing.
Researchers can then sequence the DNA of these roundworms.
the genetics of ageing
San Miguel said: “Once we have the genomic data, we can identify the mutations in C. elegans.
“And the protein aggregation and lifespan data allow us to assess which mutations may be most relevant to ageing. This allows us to focus future research on those genes.”
In proof-of-concept testing, the researchers chose to do genome sequencing on the individual roundworm in their sample that had the highest level of protein aggregation.
They found that it had a mutation on a gene that was not previously identified as having any relationship to ageing.
San Miguel added: “The next step is to do additional research focusing on this gene.
“Is it playing a role in the ageing process? And, if so, what is that role?
“More importantly, we think the technique we’ve demonstrated in this paper can be used by others in the research community to help identify genes of interest and – hopefully – expedite research into the genetics of ageing.
“We’re very open to collaborating with other researchers who are interested in pursuing this line of work.”
The research is published in iScience.
Image: Researchers from NC State University have developed a new method for determining which genes are relevant to the ageing process. The work was done in C. elegans, an animal species widely used as a model for genetic and biological research, but the finding has broader applications for research into the genetics of ageing. This image is of the head of a C. elegans showing fluorescently labelled protein aggregates. © Adriana San Miguel.