The ageing of cells may be due to errors that harm protein production

Cellular ageing could be linked to genetic errors that arise over time, a finding that may bring us a step closer to identifying drug targets that slow the process.

Payel Sen at the National Institutes of Health in Maryland previously found that control over gene expression – the process of turning information that is encoded in a gene into a function – breaks down in yeast and worm cells when they stop dividing but still produce energy, known as senescent cells. In people, previous studies have shown that the number of senescent cells increases as we age.

To uncover a potential link between impaired gene expression and senescent cells in people, Sen and her colleagues took cultured lung cells from a donated human fetus and made them divide so frequently that they became senescent in three months, mimicking the ageing process.

The team then used a sequencing method called PRO-cap to analyse the lengths of newly formed RNA transcripts, which make proteins in a cell from a gene’s DNA expression.

The researchers found that these fetal senescent cells gave rise to very short RNA transcripts. These may then fail to make proteins or may make proteins that don’t act as they should, says Sen, who hopes to investigate this further in the future.

Increased variability in the gene expression that makes these short transcripts has been linked to ageing, but we don’t know what is going on, says Sen.

“[The short transcripts] could be taking vital energy from the cell to be translated into a protein that is not useful,” she says. “But in truth, we don’t really know.”

In another part of the experiment, the researchers found similar impaired gene expression in aged liver cells from mice. “The very fact that this is conserved from yeast to mouse to human cells warrants further investigation into the mechanism’s role in ageing,” says Sen.

For now, it is unclear if senescent cells cause ageing or if ageing causes cells to become senescent, she says.

“This study shows that the precise control of transcription breaks down with ageing,” says Bérénice Benayoun at the University of Southern California. This could provide us with a new target for drug development to manipulate the ageing process, she says.

But “we also need to temper this enthusiasm”, says Jeffrey Craig at Deakin University in Australia. There are probably many aspects to ageing, such as telomere shortening, which occurs when the region of repetitive DNA at the end of a chromosome shortens over time.

“There may be no one-size-fits-all anti-ageing intervention,” he says.