Intimations of immortality? Gene manipulation could retard ageing

Researchers have identified 238 genes linked to ageing, and found that switching them off extends life in yeast cells, an advance that provides new genomic targets, which could be used to boost human lifespans.

Many of the genes are present in mammals, including humans, suggesting that switching them off could dramatically increase lifespan.

Scientists at the Buck Institute for Research on Ageing and the University of Washington identified 238 genes that, when removed, increase the replicative lifespan of S cerevisiae yeast cells.

This is the first time 189 of these genes have been linked to ageing, researchers said.

"This study looks at ageing in the context of the whole genome and gives us a more complete picture of what ageing is," said lead author Brian Kennedy, president and CEO of the Buck Institute for Research on Ageing.

Researchers examined 4,698 yeast strains, each with a single gene deletion. To determine which strains yielded increased lifespan, the researchers counted yeast cells, logging how many daughter cells a mother produced before it stopped dividing.

"We had a small needle attached to a microscope, and we used that needle to tease out the daughter cells away from the mother every time it divided and then count how many times the mother cells divides," said Kennedy.

These efforts produced a wealth of information about how different genes, and their associated pathways, modulate ageing in yeast.

Deleting a gene called LOS1 produced particularly stunning results. LOS1 helps relocate transfer RNA (tRNA), which bring amino acids to ribosomes to build proteins.

LOS1 is influenced by mTOR, a genetic master switch long associated with caloric restriction and increased lifespan. In turn, LOS1 influences Gcn4, a gene that helps govern DNA damage control.

"Calorie restriction has been known to extend lifespan for a long time. The DNA damage response is linked to ageing as well. LOS1 may be connecting these different processes," said Kennedy.

A number of the age-extending genes the team identified are also found in C elegans roundworms, indicating these mechanisms are conserved in higher organisms.

In fact, many of the anti-ageing pathways associated with yeast genes are maintained all the way to humans.

The researchers hope that, ultimately, these efforts will produce new therapies.

"Almost half of the genes we found that affect ageing are conserved in mammals," said Kennedy.

"In theory, any of these factors could be therapeutic targets to extend healthspan. What we have to do now is figure out which ones are amenable to targeting," he said.

The study was published in the journal Cell Metabolism.