Scientists let mice grow old and young again. Are humans next?


An Australian scientist seems to have cracked the code to control aging processes. It could well become the biggest science story for 2023.

David Sinclair, professor of genetics at Harvard Medical School, and a team of more than 60 researchers developed mice to age prematurely and quickly.

As Science reported: “Within weeks they lost hair and pigment; within months they showed multiple signs of fragility and tissue aging.”

Then they were made young again

Some of these lab mice were then epigenetically engineered to become young again.

Simply put, they rebooted using a youthful template of their own. (More explanation follows.)m Their muscles, eyes and kidneys seemed to reverse the aging process.

Brother and sister mice: The mouse on the right was lab-aged. Photo: David Sinclair

The experiments were then reenacted like a magic show: mice were repeatedly made old and young again.

In a Harvard statement, Dr. Sinclair said, “We hope these results will be seen as a turning point in our ability to control aging,” said Dr. Sinclair.

“This is the first study to show that we can have precise control over the biological age of a complex animal; that we can drive it forward and backward at will.

Is it as simple as it sounds?

It takes some unpacking. To begin with, the cause or main driver of aging is a matter of complex debate – with much interest in the role of UKTN, which contains our unique genetic code.

You may have heard that UKTN is called “the blueprint of life” because it contains the instructions we need to grow, develop, survive and reproduce.

So it makes sense that accumulated damage to UKTN (in the form of genetic mutations) can cause our bodies to deteriorate in the way they function, resulting in our minds, hearts, and muscles not working as well. as before. did. In other words, we are getting older.

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The issue of damaged UKTN has loomed over the issue of aging for years. Photo: Getty

And if damaged UKTN is not the root cause, then it certainly is, the argument goes, at least an accelerator of aging.

According to one theory, our old age death is programmed into our genetic code.

In other words, the UKTN that predicts and determines your eye color, height, and facial features will also determine and predict your gradual or not-so-gradual (in the case of early killer cancer) decline and exit.

Proving that this is the case is not easy. And there’s an awkward question that lingers: does UKTN damage cause aging, or does aging cause UKTN damage?

Not the full story

The Harvard researchers point to evidence that “there’s more to it.”

For example, some researchers say that “some humans and mice with high mutation rates show no signs of premature aging.”

And other studies found that “many types of senescent cells have few or no mutations.”

So the question became, “What else works with or instead of UKTN changes to cause aging?”

Epigenetics is gaining ground

One theory that is gaining traction is that epigenetics—the circuitry that turns our genes on and off—is the main cause of aging, and the key to reversing it.

Dr. Sinclair and company believe their study, which is 13 years in the making, demonstrates “for the first time that degradation in the way UKTN is organized and regulated … can cause aging in an organism independent of changes in genetic code itself”.

Dr. David Sinclair says aging may be more of a “breakdown” in the system. Photo: Getty

Epigenetics is the study of how our behavior and environment trigger changes that affect the way genes work.

Crucially, epigenetic changes are reversible, while UKTN changes (genetic mutations) are not.

How the experiment worked

According to a statement from Harvard, the team’s main experiment involved “making temporary, fast-healing cuts in the UKTN of lab mice.”

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These breaks mimicked “the low-grade, ongoing 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.”

That’s how epigenetics works.

They then tested whether aging could result from all these mundane injuries by accelerating the chromosomal breaks “to simulate life fast forward.”

The researchers were careful not to damage the genome and create genetic mutations.

Epigenetic disturbance

Some explanation here: the genome is the entire set of UKTN instructions found in a cell. This is all the information an individual needs to develop and function.

There is also the epigenome which is made up of chemical compounds that modify or mark the genome in a way that tells it what to do, where to do it and when to do it. Think of it as the epigenetic toolkit.

In the experiment, the epigenetic factors initially interrupted their normal job of regulating genes. Instead, they moved to the induced UKTN breaks to coordinate repairs.

“But as time went on, things changed,” the researchers found. These epigenetic factors became “distracted” and did not return home after recovery breaks.

Instead, the epigenome became disorganized, began to lose its original information, and thus malfunctioned. Here it seemed that the aging process was the result of disorganization.

As the authors explained, “As the mice lost their youthful epigenetic function, they began to look and act old… Cells lost their identity as muscle or skin cells, for example. Tissue function faltered. Organs failed.”

The reverse

The researchers then gave the mice a gene therapy that reversed the epigenetic changes they had caused.

It was like “rebooting a faulty computer,” said Dr. Sinclair.

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Nobel Prize winner Dr. Shinya Yamanaka discovered how to make embryonic stem cells.

Some explanation here: In 2007, Japanese biomedical researcher Dr. Shinya Yamanaka human adult skin cells to behave like embryonic or pluripotent stem cells, which can develop into any cell in the body. The work earned Dr. Yamanaka the Nobel Prize.

Central to this reprogramming were four genes, which became known as ‘Yamanaka factors’.

The age-reversal therapy delivered three of these genes — Oct4, Sox2 and Klf4, collectively called OSK — in the prematurely aged mice. Their organs and tissues regained a youthful state.

The therapy “triggered an epigenetic program that led cells to restore the epigenetic information they had when they were young,” said Dr. Sinclair.

“It’s a permanent reset.”

And this wasn’t the Harvard team’s first sensational reversal of fate for laboratory mice.

Dr Sinclair – listed below Time magazine‘s 100 Most Influential People of 2014 and the co-director of Harvard’s Paul F. Glenn Center for Biology of Aging Research – used the same cocktail of genes to restore vision to blind mice in 2020.

Harvard researchers honored blindness in mice in 2020. Photo: Getty

The human factor?

However, these are very early days – and a major step has been taken in safely translating an experiment on mice into a treatment for humans.

To begin with, reprogramming an entire human epigenome with genetic therapy carries risks, namely cancer.

But the potential for a new treatment for age-related diseases seems legitimate.

“We expect the findings to change the way we look at the aging process and the way we approach treating diseases associated with aging,” said co-first author Jae-Hyun Yang, a research fellow in genetics at Sinclair. lab.

First, the results need to be replicated in larger mammals and in humans. Studies in non-human primates are already underway.

“We hope that these results will be seen as a turning point in our ability to control aging,” said Dr. Sinclair.


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