A 13-year study by researchers at Harvard University has shown for the first time that the modification of gene expression can lead to cell ageing.

For years mainstream thinking in scientific circles has been that ageing is caused by mutations in genetic code which causes cells to malfunction and die, however, this new study, published in the journal Cell, suggests that it’s the way DNA is governed that drives ageing.

In layman’s terms, the researchers are suggesting that ageing doesn’t mean cells are damaged and incapable of behaving like young cells, but rather that something has got lost in translation in their genetic make-up. So, in theory, if we use epigenetic interventions to get cells back on the right path, they can ‘remember’ how to be young and fully functioning again – effectively reversing the ageing process.

Main experiment
In the main experiment, scientists at Harvard mimicked breaks in chromosomes that cells experience every day in response to things such as breathing, exposure to sunlight and contact with certain chemicals. They ensured these breaks did not occur in the coding regions of the DNA so mutations were prevented from occurring over time.

The team noticed that the epigenome grew disorganised leading to more aged looks and behaviour. Next, they delivered gene therapy to reverse the changes and found the organs and tissues had resumed their youthful state.

“It’s like rebooting a malfunctioning computer,” says the paper’s senior author David Sinclair, explaining that the therapy “led cells to restore the epigenetic information they had when they were young”.

A different view
Co-first author Jae-Hyun Yang adds: “We expect the findings will transform the way we view the process of ageing and the way we approach the treatment of diseases associated with ageing.”

This is because it’s easier to manipulate the molecules that control epigenetic processes rather than to reverse DNA mutations. Such interventions could include injecting stem cells to “help rewind mature cells”, for example, or using drugs.

Sinclair hopes the work inspires other scientists to study how to control ageing to prevent and eliminate age-related conditions such as frailty, cardiovascular disease and Type 2 diabetes.

The ultimate goal, he concludes, would be to address the root causes of ageing to help people live healthier lives for longer.

• Sinclair, D. et al. Loss of epigenetic information as a cause of mammalian aging. Cell, January 2023