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Epigenetic Engineering Rejuvenates Lab Mice

19 January 2023
Giulio Prisco

Lab Mouse

Scientists led by Harvard Medical School have shown that degradation in the way DNA is organized and regulated - known as epigenetics - can drive aging in an organism, independently of changes to the genetic code itself.

“We believe ours is the first study to show epigenetic change as a primary driver of aging in mammals,” says research leader David Sinclair in a press release issued by Harvard Medical School.

A story published in Time Magazine explains that epigenetic information is what makes skin cells turn into skin cells and brain cells into brain cells. “It does this by providing different instructions to different cells for which genes to turn on, and which to keep silent.” Epigenetics “is like a cell’s operating system, telling it how to use the same genetic material differently,” notes one of the scientists in the press release.

In a research paper published in Cell, the scientists report that, by manipulating the epigenome, aging can be driven forward and backward. Not only were the scientists able to age mice on an accelerated timeline, but they could also reverse the effects of that aging and restore some of the biological signs of youthfulness to the animals.

The scientists experimented with laboratory mice. First, the scientists used a technology platform called ICE (Inducible Changes to the Epigenome) to accelerate the breaks in chromosomes that mammalian cells experience every day in response to things like breathing, exposure to sunlight and cosmic rays, and contact with certain chemicals. The mice began to look and act old. Quantitatively, an aging clock developed by the scientists revealed a rise in biomarkers that indicate aging.

Then, the scientists gave the mice a gene therapy that reversed the epigenetic changes they’d caused. The gene therapy delivered three genes that are active in stem cells and can help rewind mature cells to an earlier state. The mice’s organs and tissues resumed a youthful state. The therapy “set in motion an epigenetic program that led cells to restore the epigenetic information they had when they were young,” says Sinclair. “It’s a permanent reset ... like rebooting a malfunctioning computer.”

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

The findings show that a breakdown in epigenetic information causes mice to age and that restoring the integrity of the epigenome reverses those signs of aging. The findings also support the hypothesis that mammalian cells maintain a kind of backup copy of epigenetic software that, when accessed, can allow an aged, epigenetically scrambled cell to reboot into a youthful, healthy state.

Of course, medical applications are a long way off and will take extensive experiments in multiple cell and animal models. But Sinclair is persuaded that scientists should think big and keep trying in order to achieve such dreams.

The scientists were able to rejuvenate cells in mice. But will the process work in humans? That, as reported by Time Magazine, is Sinclair’s next step. The scientists are already testing the system in non-human primates.

“We don’t understand how rejuvenation really works, but we know it works,” concludes Sinclair as reported by Time Magazine. “We can use it to rejuvenate parts of the body and hopefully make medicines that will be revolutionary. Now, when I see an older person, I don’t look at them as old, I just look at them as someone whose system needs to be rebooted. It’s no longer a question of if rejuvenation is possible, but a question of when.”

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