Biology

Epigenetic "reboot" reverses aging in mice and could extend lifespan

Epigenetic "reboot" reverses aging in mice and could extend lifespan
Two mice of the same age, but the mouse on the right has undergone an epigenetic experiment that accelerates its aging. Luckily, this process can also be reversed, according to new work
Two mice of the same age, but the mouse on the right has undergone an epigenetic experiment that accelerates its aging. Luckily, this process can also be reversed, according to new work.
View 1 Image
Two mice of the same age, but the mouse on the right has undergone an epigenetic experiment that accelerates its aging. Luckily, this process can also be reversed, according to new work
1/1
Two mice of the same age, but the mouse on the right has undergone an epigenetic experiment that accelerates its aging. Luckily, this process can also be reversed, according to new work.

Scientists at Harvard Medical School have investigated why we age, and identified a possible way to reverse it. In tests in mice, the team showed that epigenetic “software glitches” drive the symptoms of aging – and a system reboot can reverse them, potentially extending lifespan.

Our genome contains our complete DNA blueprint, which is found in every single cell of our bodies. But it’s not the whole picture – an extra layer of information, known as the epigenome, sits above that and controls which genes are switched on and off in different types of cells. It’s as though every cell in our body is working from the same operating manual (the genome), but the epigenome is like a table of contents that directs different cells to different chapters (genes). After all, lung cells need very different instructions to heart cells.

Environmental and lifestyle factors like diet, exercise and even childhood experiences could change epigenetic expression over our lifetimes. Epigenetic changes have been linked to the rate of biological aging, but whether they drove the symptoms of aging or were a symptom themselves remained unclear.

For the new study, researchers at Harvard conducted experiments in mice to find out. Using a system called inducible changes to the epigenome (ICE), the team sped up the natural process of DNA damage and repair in mice, to check whether this also accelerated aging symptoms.

If correct, it means that cancer, diabetes and Alzheimer's might have the same underlying cause that can be reversed to treat or cure age-related conditions with a single treatment

In mammal cells, our chromosomes experience as many as a million DNA breaks per minute, and epigenetic factors very quickly coordinate repairs before returning to their original locations. The team engineered mice that experience DNA breaks at a rate of three times faster than normal.

Over time, they found that the epigenetic factors became more “distracted” and wouldn’t return home after they repaired the DNA breaks, leading to the epigenome becoming jumbled. Sure enough, by the age of six months the mice showed the physical signs of aging, appearing to be in much worse health compared to unedited mice of the same age.

With this, the scientists say they’ve confirmed the role of the epigenome in aging. The next step was to test whether we can do anything about it, so the team administered a gene therapy cocktail of three genes, known as Oct4, Sox2 and Klf4. These are active in stem cells, and in previous work the team found that they could be used to restore vision to mice with age-related glaucoma.

In this case, the ICE mice experienced a dramatic reduction in biomarkers of aging. Their epigenomes became unscrambled and returned their tissues and organs to a more youthful state.

“It’s like rebooting a malfunctioning computer,” said David Sinclair, senior author of the study. “[It] set in motion an epigenetic program that led cells to restore the epigenetic information they had when they were young. It’s a permanent reset.”

This discovery is potentially huge, the team says. By tackling aging itself, many diseases that arise out of this natural process could be treated more effectively.

“If correct, it means that cancer, diabetes and Alzheimer's might have the same underlying cause that can be reversed to treat or cure age-related conditions with a single treatment,” Sinclair posted on Twitter.

While there’s still plenty more research to be done before such lofty goals could be realized, work is already underway. A preprint paper, yet to be peer reviewed, administered the same gene therapy cocktail systemically to elderly mice, at an age equivalent to 77 years old in humans. These mice lived 9% longer than untreated mice.

The new study was published in the journal Cell. The team describes the work in the video below.

Epigenetics and Aging: The effects of DNA breakage and repair

Source: Harvard Medical School

14 comments
14 comments
guzmanchinky
Well, I'm 52 and supposedly healthy (bi-yearly scans and yearly bloodwork), so maybe, just maybe, I'm young enough to where I might see some benefits from this kind of science! Here's hoping (but not holding my breath!)...
rlseifer
I turn 90 later this year. Can these mice be barbecued, and if yes, how many do I need to eat to get another 15 or 20 years??
nummitz
Of course, the answer to everything is: “have you tried turning it off and on again”.
Sean Stuart
Off and on... The implications are scary. Millions of 170 year olds who will do anything to keep from being turned off. 1984, meet 2084
Lamar Havard
Where can I get THAT vaccine?
mark34
If this is true then the planet is going to become very crowded.... there's a reason that we all have a 'Best Before' date (and an expiry date too!)
sidmehta
After all the hyperbole (reboot, reverse aging) at the end, the article says lifespan increased by only 9%.
Louis Vaughn
9%, so 70 becomes 76; more time to suffer as our life force declines. Forget lifespan;
will I look 20 again? Will my senses become sharp again? How about my stamina? Will my congestive heart failure be reversed (without surgery)? Will I be able to walk with a healthy gait, And, will all the aches and pains go away? Will my end-of-life be joyful bliss or drugged misery. Quality over Quantity rules!
Themadcow
People talking about quality over quantity... yes, that's exactly what this article is claiming. Regeneration of organs and tissue to a healthy state, not merely the elongation of lifespan. However, I do share the concern that taken to it's conclusion, the implications of extending life through regenerative organs are quite scary when you look at the current global challenges we face.
Eggster
My understanding is that epigenetic factors are like bookmarks. One type is like a clip or rubber band placed upon pages of a reference manual that are no longer needed, whereas others are like an actual bookmark or reference tag that are placed upon pages that are referenced frequently.

Is that a fair description?
Load More