Ageing reversed in mice in groundbreaking study

Scientists have managed to reverse the process of ageing in mice, raising questions over whether the same could one day be done for humans.

Researchers at Harvard Medical School also found a way to speed up the biological process, suggesting it can be driven “forwards and backwards at will”.

The key to this, scientists found, is manipulating the rodents’ epigenomes – which function as an operating system by instructing cells how to interpret and use genetic material.

It is easier to tweak the molecules that drive the body’s epigenetic process than to reverse DNA mutations, say researchers, opening up a raft of possibilities in how ageing could one day be treated.

The findings, published on Thursday in the scientific journal, Cell, challenge the idea that ageing is the result of genetic mutations that break down our DNA and lead to deterioration.

“It’s not junk, it’s not damage that causes us to get old,” said David Sinclair, a professor of genetics in the Blavatnik Institute at Harvard Medical School.

He told CNN: “We believe it’s a loss of information — a loss in the cell’s ability to read its original DNA so it forgets how to function — in much the same way an old computer may develop corrupted software. I call it the information theory of ageing.”

Scientists found that by making chemical and structural changes to chromatin — the complex of DNA and proteins that forms chromosomes, they could fuel the ageing process without altering genetic code.

Next, researchers gave the mice a gene therapy that reversed the epigenetic changes they’d made, described by Prof. Sinclair as like “rebooting a malfunctioning computer”.

By delivering a trio of genes, known in combination as OSK, which are active in stem cells, they were able to restore the cells in the mice’s organs and tissues to a more youthful state.

Prof. Sinclair says the findings support the hypothesis that mammalian cells carry a backup copy of epigenetic “software” that can reboot an aged and degraded cell.

“We hope these results are seen as a turning point in our ability to control aging,” he added.

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“This is the first study showing that we can have precise control of the biological age of a complex animal; that we can drive it forwards and backwards at will.”

We are still a long way off before this kind of treatment could ever be carried out on humans.

First, the results will have to be replicated in larger mammals, although studies in nonhuman primates are already underway.

Researchers could also one day find other methods beyond OSK gene therapy to restore lost epigenetic information.

“There are other ways to manipulate the epigenome, like drugs and small molecule chemicals that induce gentle stress,” said Jae-Hyun Yang, a genetics research fellow at Harvard’s Sinclair Lab and the paper’s co-author.

“This work opens a door for applying those other methods to rejuvenate cells and tissues.”