4,000 years ago, an anonymous Sumerian wrote the first work of fiction that would survive to this day, the epic of Gilgamesh, which tells of the adventures of a king who seeks immortality. It is not a coincidence: lengthening our expiration date has always been a very human obsession, which is why we have found it since the beginning of history.
Over the centuries, that impossible dream has gone from being the heritage of fiction to becoming an increasingly real possibility. It has been thanks to a series of discoveries that have allowed us to understand the key to the problem: why we age.
The simplest answer: because our cells age. Although this change in perspective may seem trivial, jumping from the visible to the microscopic world offers us many possibilities.
Eliminate old cells to slow down aging
Aging had traditionally been seen as inevitable, a consequence of being alive. But over time we have discovered organisms that seem immortal, such as hydra or certain jellyfish, capable of regenerating indefinitely. Others age at an extremely slow rate, like whales.
This made us think that the progressive degeneration that our bodies undergo from the fourth decade of life had to be explained by biological mechanisms that function at different rates according to each species.
Indeed, after years of research they have defined nine factors which are believed to be the main responsible for the aging of tissues and, therefore, determine the effects of the passage of time in our bodies.
Beyond the simple curiosity of knowing how things work, this has a clear utility: once we have identified the details of a process, we are in a position to modify it.
Several strategies are currently being tested in the laboratory. From lengthening telomeres to recovering stem cells or reducing oxidative damage. But the one that seems to have the best chance of success is eliminating old cells, also known as senescents.
Many of the processes that lead to aging end up generating these senescent cells that, little by little, fill the tissues. This evolution prevents the rest of the cells from doing their usual tasks, which is why the organs stop working properly.
This was confirmed ten years ago generating a transgenic mouse in which senescent cells could be destroyed at will. The result was that the animals lived longer and with a better quality of life.
An effective drug with too many adverse effects
The race to find how to do the same in humans began immediately. It took little time to find a new class of drugs, senolytics, which had the ability to kill senescent cells without affecting normal cells too much.
It was shown that improved health of laboratory animals. Then clinical trials were launched to look at what effects they have in diseases related to aging in which it has been seen that there is an excess of senescent cells.
But senolytics are, after all, well-known chemicals that were used for other things. Thus, their specificity is relative, and they have more side effects than would be desirable. That is, they serve as a first step, but safer alternatives must be found if they are to be used to treat the symptoms of aging.
More precise drugs targeting target cells
This is where the second generation of senolytics would come in, which are being designed in groups such as the University of Leicester (UoL) and the Open University of Catalonia (UOC). It’s about making tools that accurately recognize target cells and destroy them without touching their neighbors. This is what are called targeted therapies.
There are several ways to do it. It occurred to the Uol / UOC team to start by investigating what the senescent cell surface looks like, what characteristic protrusions it has that other cells do not have and that can be easily identified.
After get this, we went on to the second phase: building something that could hook onto one of those protrusions and discharge a toxic substance into the cell. It is not a new concept: something similar is already being used to treat cancer. That is, it was decided to copy an idea that worked well and adapt it to another field.
That’s how has been built what is called a “smart bomb”, tuning an antibody so that, instead of recognizing a microbe or a cancer cell, it looks for the senescent cell, latches on to its surface and “explodes” inside it.
Will it work in humans?
So far the idea has been shown to work in cultured human cells. Now we have to see what effect it has on an organism and, especially, if there are any undesirable consequences. If the next animal experiments work, it would move on to testing it in humans.
In theory, these targeted senolytics should effectively reduce the load of old cells in tissues and slow the aging process, at least in certain situations.
This will not give us immortality, naturally, nor is it intended, but it could reduce the ill health that many people have to endure in the final stretch of their lives. Surely even Gilgamesh would gladly join.