up the ascending stairs

The institute's scientists have identified the enzyme that cuts the proteins that create the blockages. The discovery may help treat diseases that cause accelerated aging, in which such blockages are involved.

There are those for whom the road is fast, and he qualifies with quick steps up the escalators - at the airport, in an office building or in a shopping mall - and in such a case, his climbing speed is added to the escalator's constant rate of ascent. When a similar process takes place in the systems that determine the body's aging rate, the person ages at an accelerated rate. This is exactly what happens in the bodies of children suffering from the disease called progeria. A similar phenomenon was described in the film "Jack" by Francis Ford Coppola, in which Robin Williams starred. In the film, as often in films, there are funny-sad, sour-sweet situations. But in real life it is a tragedy: this disease causes two-year-old toddlers to age, and when they are 12 they die, like old people.

Studies in which the genetic root of the disease was examined pointed to a central cause of accelerated aging. Now a new study by Weizmann Institute of Science scientists, which examined a completely different question, may shed additional light on the causes of the disease, and in the future may even help delay the aging process.

The present study began when Prof. Maya Schuldiner, and the members of the research group she heads, wanted to test communication processes between cells. "The ability to send and receive signals from neighboring cells and the environment is essential, and without it there would be no life," says Prof. Shuldiner. "In fact, 30% of the energy of every living cell is invested in carrying out communication processes." A significant part of the communication processes between cells is carried out using proteins, some of which receive signals (receptors placed on the cell membranes), and some of which are sent out from the cell, as messages.

The proteins that are supposed to be secreted from the cell, as messages to other cells, were at the center of Prof. Shuldiner's research and the members of her group. These proteins are transferred - as soon as they are created by the ribosome - to a "transition area" in the cell, from where they are secreted out. The transit area is bounded by a sort of "fence" that separates the active inner space of the cell ("cytoplasm") from the "transit platform", reminiscent of an area where a military force is organized before going into action, or where passengers, who have already been checked, are waiting to board a plane. In this fence there are a kind of tunnels, through which the young proteins pass, which are in a chain configuration, even before they fold into their characteristic three-dimensional spatial structure.

"When the young protein begins to pass through the tunnel, it is pulled in by proteins that do not allow it to go back," says Prof. Schuldiner. "Sometimes, if a part of the protein that has not yet passed, and is still in the cytoplasm, begins to fold, it fails to pass through the tunnel - and the protein gets stuck." This creates a kind of blockage, which not only does not allow the protein to pass, but also puts the tunnel out of action. When this phenomenon takes place in many tunnels, the cell gets into trouble, because it cannot receive or transmit signals, which in some cases can cause its death.

The main question that preoccupied the scientists was, how does the cell manage to overcome the "clogging" of the tunnel with a protein that binds on one side, and begins to fold on the other side. To answer it, they engineered yeast cells to express more of the protein that creates blockages in the tunnels. The experiment was carried out on 6,200 types of yeast cells, each of which lacks or silences a different gene (the yeast genome contains 6,200 genes). In this way, the scientists reported In a recently published article in the scientific journal Cell, they managed to identify the protein that fulfills the role of the "plumber". It is a protease-type enzyme, which cuts the protein that causes a blockage - thus freeing the tunnel so that it can continue to function. At this stage, the scientists engineered yeast cells so that they lacked the "plumber" protein, and as a result, the cells lacking the "plumber" proteins suffered from blocked tunnels, and had difficulty secreting communication proteins, which led to their death.

Prof. Schuldiner says that the "plumber" protein is well conserved throughout evolution; That is, there is almost no difference between this protein in yeast cells and its version found in human cells. Indeed, when the scientists implanted the human gene encoding this protein into yeast cells, the cells produced the human protein - which functioned well in the yeast cells.

Here we can return to the disease of accelerated aging. In human cells, when the activity of the "plumber" protein is inhibited, blockages are formed in the tunnels, and at the same time aging processes are accelerated. From this arises the possibility that normal aging processes also result to a certain extent from the "fatigue of the material" and a slowdown in the activity of the "plumber" protein. If so, it is possible that if a way is found to stimulate the "plumber" protein (or if a replacement is found for it), it will improve and optimize the secretion processes - and slow down aging.