Rejuvenation via epigenetic modification

[corybroo]

Here’s an article with a rather bold claim. 

“For now, the extensive experiments led the team to conclude that "by manipulating the epigenome, aging can be driven forwards and backwards," said Yang.”

To be fair, the rejuvenation was done in rats that had been artificially aged.

Loss of epigenetic information can drive aging, restoration can reverse it

 

"We believe ours is the first study to show epigenetic change as a primary driver of aging in mammals," said the paper's senior author, David Sinclair, professor of genetics in the Blavatnik Institute at Harvard Medical School

The team's extensive series of experiments provide long-awaited confirmation that DNA changes are not the only—or even the main—cause of aging. Rather, the findings show, chemical and structural changes to chromatin—the complex of DNA and proteins that forms chromosomes—fuel aging without altering the genetic code itself.

some researchers found that some people and mice with high mutation rates don't show signs of premature aging. Others observed that many types of aged cells have few or no mutations.

The team's main experiment involved creating temporary, fast-healing cuts in the DNA of lab mice.

In the study, to test whether aging results from this process, the researchers sped the number of breaks to simulate life on fast-forward.

The team also ensured that most of the breaks were not made within the coding regions of the mice's DNA—the segments that make up genes. This prevented the animals' genes from developing mutations. Instead, the breaks altered the way DNA is folded.

At first, epigenetic factors paused their normal job of regulating genes and moved to the DNA breaks to coordinate repairs. Afterward, the factors returned to their original locations.

But as time passed, things changed. The researchers noticed that these factors got "distracted" and did not return home after repairing breaks. 

As the mice lost their youthful epigenetic function, they began to look and act old. The researchers saw a rise in biomarkers that indicate aging.

Sinclair's lab [measured] how old the mice were, not chronologically, in days or months, but "biologically," based on how many sites across the genome lost the methyl groups normally attached to them.

Next, the researchers gave the mice a gene therapy that reversed the epigenetic changes they'd caused.

Because signs of aging developed in the ICE mice after only six months rather than toward the end of the average mouse life span of two and a half years, the approach also saves time and money for researchers studying aging.  [But doesn’t prove that mice that aged normally would behave the same.  CB]

The goal would be to address the root causes of aging to extend human health span: the number of years that a person remains not just alive but well.

Medical applications are a long way off and will take extensive experiments in multiple cell and animal models. 

[mccoy]

If I'm not wrong, these techniques involve the use of 3 of the 4 so called Yamanaka's factors, proteins which can reprogram an old cell back to a pluripotent stem cell. This equals to reverse aging (for the cell) taking it back to zero years.  Only 3 of the factors are generally used, since a partial reprogramming is safer, the risk being that an aggressive epigenetic interventions creates tumors.

Practical applications for humans are still non existent. If a technology to use these factors is developed, it must be absolutely safe, since we cannot waste so many human beings who became full of tumors as we can do with lab mice. They don't tell it, but for  successful experiment there are probably who knows how many dead rats left behind...

 

Edited January 13, 2023 by mccoy