To stop death - part three: the hunger for life

In recent records we learned that when longevity is achieved through genetic improvement, it causes the metabolism to slow down, at the expense of fertility and the bursting energy of youth.

In recent records we learned that when longevity is achieved through genetic improvement, it causes the metabolism to slow down, at the expense of fertility and the bursting energy of youth. It turns out that there are also those who are willing to pay this price - to give up fertility - in order to gain a few more decades towards the end of their lives.

The first to actively decide to do this was a Venetian nobleman named Luigi Cornaro who published in 1550 a book called Discorsi della vita sobria - a discussion on the sober life - in which he told about a special diet regime he had invented himself and was supposed to prolong his life.

Here is a picture of foods that would find their place on a typical dinner table today. You can see different types of meat, vegetables, fruits, bread, eggs, milk and more. What do you think Cornaro chose to cut from his menu?

In fact, Cornaro decided not to rule out one particular food item, but simply: eat less, and only eat what tastes good. In his book he said that he usually eats bread, porridge, eggs, veal, pork, chicken and fish. In short, at least in terms of quality he didn't hurt himself too much. But the quantity, gentlemen, the quantity! There he really cut, up to about a thousand calories a day - less than what Jewish prisoners received in some of the concentration camps at the beginning of the Holocaust.

If we look at data from around the world at that time (England, New England, Virginia), life expectancy was 35 years for the rich, and 25 years for the poor. This statistic does not necessarily mean much, because it includes the children who died at a young age - about 40% of the population. But if we look at a person who managed to get through childhood, we will find that he gets an average of 47 years of life.

How many years did Cornaro live?

The answer is that he wrote his book at the age of 83. And he continued to live and write, until he died at the age of 99. For his contemporaries, he was like a god. like Methuselah. He called them to eat less... and he was probably right.

Dozens of studies have already shown that the only effective way to extend the lifespan of a mouse is to provide it with up to 50% of the food ration of its friends. Mice on this diet are more alert and healthier than their peers. Eventually they die, of course, but the ages at which they are afflicted with diabetes, inflammation, kidney failure, auto-immune diseases, muscle atrophy, heart disease, neurodegeneration - all of these are inhibited. And most amazing of all, even cancer is inhibited in them. Research is currently being conducted on rhesus monkeys to see how they react to starvation, but it will take at least another decade before we know the answer.

When it comes to humans, such a diet should provide about a thousand calories per day - which is the upper limit that is sufficient to sustain the body. This is a starvation diet in all its most difficult meanings, and very few people will be able to withstand such a diet for a long time of their own free will. And although this diet is enough to fuel the body, it certainly does not support the sexual drive.

It is not clear exactly why it works, but at least one explanation has to do with the effects we have already seen that Rabia has on the aging process. Animals undergoing a starvation diet have fewer offspring. It is possible that the energy saving that comes from ceasing childbirth helps prolong life. But apparently that's not all. In flies undergoing a starvation diet, most of the genes involved in reproduction are silenced - but other genes are activated at their peak. Such increased genes, for example, strengthen the immune system. This could explain the resistance that the mice on the cancer diets develop, for example, because the immune system is able to locate cancer cells and kill them more efficiently. But this is probably only a small part of the picture. Of the 15,000 genes a fly has, about XNUMX of them respond in one way or another to the starvation diet it undergoes. It is quite possible that the starvation diet works through the combined effect of dozens of different metabolic and molecular pathways.

So we have one clear solution - the starvation diet. Unfortunately, it is clear that this solution is far from optimal. None of us wants to starve to stay alive. Still, this is the only way to activate the anti-aging genes.

But what if we could activate these genes without starving the body? What if we could reach into the deepest mechanisms in the cells - skip the activation signal coming from the starvation diet - and directly activate the aging-inhibiting genes?

Genetic engineering to mimic starvation

We know from previous studies that the SIRT3 gene is activated during controlled starvation. In a new study published in recent weeks, its action was tested in blood stem cells. These stem cells constantly renew the supply of red blood cells and white blood cells: those that carry oxygen in the body to the cells, and those that protect the body from foreign invaders. The tests conducted showed that SIRT3 helps the tissue cope with stressful conditions. When the SIRT3 gene was inserted into the blood stem cells (which are responsible for the production of blood cells, such as red blood cells and white blood cells), the treatment caused an increased production of new blood cells - an ability that the stem cells are usually endowed with in their youth.

The researchers used genetic engineering to increase the levels of SIRT3 in the blood stem cells of elderly mice, and witnessed a miraculous phenomenon: the treatment restored the youth of the aging cells, and they produced larger amounts of blood cells.

Is this treatment for life extension? There is no answer to that yet. The researchers did not wait to see if the lifespan of the mice increased. However, since the aging process is a combination of many small injuries in the different mechanisms of the body, it seems logical that correcting one of the mechanisms will help prolong life.

"We already knew that sirtulines [the group of genes to which SIRT3 belongs] control aging, but our study demonstrates for the first time that sirtulines can reverse the degeneration associated with aging, and I think that's very exciting." said lead researcher Danica Chen, a professor at UC Berkeley. "The research opens the door to potential treatments for age-related degenerative diseases."

And really, how close is the treatment to humans? As with any genetic engineering treatment, it is hard to believe that ordinary people - that is, those who are not suffering from serious diseases - will receive permission to change their own genetics. Even if a medical treatment is developed as a result of the research, in the next decade it will only serve as a way to help elderly patients produce a large number of red blood cells and white blood cells. But even this type of treatment still has a long way to go.

One of the biggest concerns, as always, is that the game in the genetics of the cells - each of which is an elaborate and complex machine, controlled by the genes - could cause them to get out of control and create a cancerous growth. In this case, SIRT3 actually has one big advantage: previous studies have identified that it plays a role in taking over the cell, preventing it from becoming a cancer cell. Therefore, a medical treatment that combines the introduction of SIRT3 into the cells may help both in restoring youth - and in reducing the danger of developing cancerous tumors.

A door closes, a window opens

The sirtuline family is just one of the gene families that are activated during controlled starvation. The evidence indicates that the role of another piece in the complex puzzle that is the body's aging process has been revealed, but the number of pieces is still very large. It may be almost pointless to try to track each and every gene involved in the aging process, and instead we would be better off understanding how the various genes thwart aging - and perhaps inventing our own drugs that do the same thing. And hence the question arises: what does SIRT3 do?

The current suspicion is that SIRT3 protects cells from a particularly destructive class of molecules, which the next post will focus on: free radicals.