Researchers Unveil Technique for Potentially Identifying Key Aging-Related Genes

New work by researchers from North Carolina State University has revealed a novel method that could help to figure out the genes that play a critical role in the aging process.

Caenorhabditis elegans

Caenorhabditis elegans

The research, which was done in an organism that is commonly used in biological studies, appeared in the journal iScience.

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There are numerous genes that scientists do not yet know their functions. Researchers do not know, in particular, their roles in the aging process. This is according to Adriana San Miguel, the corresponding author of this study.

“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,” explained San Miguel, who is an assistant chemical and biomolecular engineering professor at NC State.

That is a problem because existing techniques for studying genes require that the animals to be used should still be able to reproduce.

This new method could be applied broadly for research probing the genetics of aging.

A new way to identify aging-related genes

Given the challenge, these NC State researchers wanted to find an alternative approach that could speed up research into genes relevant to aging. They were interested in identifying a method that would enable research while organisms are still young.

The team honed in on Caenorhabditis Elegans (simply C. Elegans) in this work. This roundworm species is used widely in genetics and aging research.

More specifically, the researchers centered their attention on the aggregation of proteins in cells. It has been proven in multiple studies that protein aggregation is pertinent to aging.

To develop the new technique, these scientists began by inducing random genetic mutations in thousands of C. Elegans through exposure to a chemical. They then made use of a self-regulating, high-throughput system to identify roundworms with high protein aggregation levels in their cells but remaining unharmed and young enough to still reproduce.

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The team isolated roundworms that showed higher degrees of protein aggregation and so expected to live for a shorter time. It then took time to observe how long these organisms would live. Researchers determined protein aggregation and lifespan data for each of the worms after they died.

Scientists can prioritize for study the roundworms that show the highest protein aggregation and shortest life spans. This is because mutations increased the likelihood of adverse effects on aging.

The DNA of the roundworms can then be sequenced for examination.

“Once we have the genomic data, we can identify the mutations in C. Elegans,” said San Miguel. “And the protein aggregation and the lifespan data allow us to assess which mutations may be more relevant to aging.”

The corresponding author noted that this will enable focus on the relevant genes in future research.

Expediting aging research

The research team went further to carry out genome sequencing on the roundworm in its sample that showed the highest protein aggregation level in proof-of-concept testing. It discovered a mutation in a gene that was previously not known to have anything to do with aging.

The method that was demonstrated in this new work can be applied broadly to genetics research, the NC State scientists hoped. The researchers said the technique could be used to identify “genes of interest” and advance research into the genetics of aging.

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San Miguel and her colleagues expressed their readiness to work with other researchers who have an interest in this line of study.

The next step is to carry out more research on the gene found to be relevant to aging in this work, according to the team. It is important to know what specific role if any, it plays in the aging process.

References

https://www.cell.com/iscience/pdf/S2589-0042(22)01732-1.pdf

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