Old mice rejuvenated with a new drug

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2017-04-14 16:15:48

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Old mice rejuvenated with a new drug

In the life of a cell is something horrible. Like the young heroes of the popular teen novels, the cells are born simply "companies" of the authority is to perform certain roles, predefined expression of their DNA. As the body in which they live, cells have a limited life expectancy and aging begin to pass toxic molecules into their surroundings.

To protect the body the older cells make the ultimate sacrifice: these include the molecular mechanism that leads to their own death. This process is called "apoptosis", which translated from Greek means "soft fall".

But sometimes aging cells cheat. Instead of trying to commit suicide, these cells are hiding in our hearts, liver, kidneys and brain, where they silently contribute to the disease. Scientists have long suspected that these "senescent" cells cause aging, but to get rid of them without causing harm to normal healthy cells, it was difficult.

And now, a joint effort of Erasmus University in the Netherlands and the Institute for research on ageing Tank in California, scientists may have found a solution. The article posted in the journal Cell, they describe a chemical torpedo, which after injection the mice finds the aging of cells and prevents them from suffering, leaving only healthy cells.

"for the First time shown that it is possible to get rid of senescent cells without any side effects," says Francis Roder of the University of Montreal in Canada who was not involved in the study.

In the treatment of this drug older mice changed their fur on a rare luxurious coat and showed improvement of liver and kidney. They also seemed more energetic, preferring to spend his time running in the wheel, not sleeping in a corner.

Instead of synthetic chemical drug is a small peptide comprised of amino acids, the building blocks of protein. Such peptide drugs have become revolutionary in the treatment of stroke, and in the near future, the team plans to begin testing the secure of the drug on humans.

The Study offers the first glimmer of hope that the elimination of senescent cells can rejuvenate people. It's definitely important and the right time.

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the Dark side

As we age, our cells accumulate damage to their DNA. Although cells have molecular "mechanisms" that can rule a small problem, eventually the damage becomes too severe and the cell is faced with a choice: to self-destruct, to become malignant or to hibernate, become senescent cell.

Initially, the aging cell was considered useful because it prevented the formation of dangerous tumors. But about ten years ago the picture changed.

"it turned Out that these senescent cells produce a whole tank of debris and they are not just there, but have a negative effect," explains the study's lead author Dr. Pieter de Keyser.

However, it remained unclear whether this accelerates the dark side of aging cells aging.

Last year, scientists from the Mayo clinic in Minnesota genetically modified mice so that their bodies automatically eliminated 50-70% of senescent cells. After six months of treatment kidney of mice became more healthy hearts, too, and, most remarkably, they lived 20% longer than their control counterparts.

Even the scientists were shocked, noting that he did not expect such a dramatic improvement. The study stirred up the entire industry: senescent cells contribute to aging. And if they can be stopped, perhaps we could also slow down the clock of aging.

The Question for a billion dollars was put like this: how to make this process work for the people, without resorting to gene therapy?

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Breaking ties

Team de Keyser came up with a brilliant solution: find out what keeps aging cells from committing suicide, and destroy the brake.

Looking at the movement of molecules within senescent cells, the team came to the strategy of the attack. Cells that carry DNA mutations typically activate protein p53, which triggers the whole program of apoptosis. However, senescent cells have another protein — FOXO4 — which snaps on the cuffs as p53, allowing p53 to do its job.

Therefore, the group has developed a peptide drug which makes its way between FOXO4 and p53. Protein is the death is released and convinces the cell to self-destruct. Because healthy cells have a very low level of FOXO4, or even zero, they are spared from the effect of the medicine.

Here's another important point: peptide drugs are usually too big to get into cells, so the market is so few of them. The team relied on a technology that has become popular not so long ago: penetrating into the cell peptides. These peptides, as their name implies, can make their way into the organs and cells after injection (even in the brain!). This is excellent for human use.

First, the group checked out your peptide to mutant mice, which had aged abnormally fast. Being only in middle age, these mice on treatment were in a poor state: their fur was stained, posture hunched, and in General they were weak and fragile.

Through four weeks of peptide injection, the mice dramatically transformed.

Although originally in hair loss no one planned to pay attention, the change was so radical, that it was impossible to ignore. The assistant ran into my office and said, "the mice had grown hair we've never seen before," says de Keyser.

On the drug rebooted the waste the kidneys of mice that they had to filter the toxic chemicals in the blood. Mice also cheered. Instead of sleeping all day in the corner of the cage, they chose a fierce race at the wheel — about five kilometers a day, which is four times more distance, which ran the control animals treated with PBS, inactive solution used to dissolve the peptide.

Imagine that a weak, elderly man suddenly jumps down from the couch, turns off the TV and voluntarily runs a marathon — and all because of a few doses of the drug.

In the following set of experiments, the authors repeated the treatment on the normal aging mice and saw a similar improvement in the kidneys and in the desire to explore the world. Not content with only one problem of ageing, the team also tested its product on animals, which was given regular chemotherapy, which causes damage to DNA and aging cells. Again, a peptide drug worked magically, eliminated the damaging effects of chemotherapy and helped the mice to support the weight of his body.

This peptide, apparently, is "a potent drug for losing health in the process of natural aging," concluded the authors. He can change the principles of our struggle with aging cells and diseases that they cause.

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From mice to men

Compared with the genetic destruction of senescent cells, and use peptide drug is much easier on people. But this does not mean that it would be quite simple. Because our stomach acid is easily chews peptides, to turn the drug into a tablet required the solution of serious problems — although we can say that the daily or weekly injection is a small price to pay for improved health and a long life span.

More relevant is the question of security. Because the peptide will be mainly given to the elderly, the risk is very high. Previous attempts to develop drugs for aging cells — sinaitici — eclipsed serious side effects.

The Team plans first to check the safety of the peptide in people with aggressive form of brain tumor, which separates the markers of aging with senile cells. "We will move carefully, first try, and then expand the circle," says de Keyser.

"If the drug is safe, we will think about the testing for the diseases associated with aging, or aging," he adds.

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