Fundamental Science: The Search for the Fountain of Youth

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In the summer of 1740, when Professor Abraham Trembley was looking for insects in the lake of his castle in The Hague, he came across an unusual finding: fixed on plants, there were tiny beings with a greenish color and the appearance of polyps that contracted when touched. The naturalist collected them, examined them with a magnifying glass and observed that they had a cylindrical body and six to eight tentacles at one end. He then carried out experiments to understand the functioning of those organisms and was ecstatic: if cut, the tentacles would grow again, reaching complete regeneration! Figuring that the scientific community at the time would not believe this, Trembley sent live polyps to other researchers and described them in detail.

Freshwater polyps have been called “hydras” and studied by countless scientists. In 1991, the young American Daniel Martinez collected dozens of hydras and began to cultivate them to assess their reproduction and mortality rates. Years passed and the hydras didn’t die… Martinez then published his findings, showing that there are no signs of aging in the hydras, which are potentially immortal. Today they are cultivated in several laboratories around the world and used as models for the study of regenerative biology. Most of the cells of this fascinating animal are stem cells that can originate all the cell types that the hydra needs, rebuilding any part of its body.

Human beings, on the other hand, have a small and limited stock of stem cells, which age over time. The first cells of a human embryo have the instructions necessary to generate all the parts of the body, but as the embryo develops, this potential becomes more restricted. Our adult skin regenerates after a small superficial cut, but we can’t rebuild all the tissues from large injuries, nor replace lost organs or limbs.

Have you ever thought if it was possible to rescue the most primitive instructions and conditions of our embryonic period, remaking damaged body parts and replacing aged cells? Recovering the human body in an increasingly efficient way is a challenge that moves many research groups around the world.

Imagine that a person who needed to replace parts of his heart could be treated with cells from his own skin. In a laboratory, the cells would be reprogrammed to an embryonic stage, and then subjected to the conditions necessary to transform into the various cell types that shape the heart’s structures. The big problem is that turning back the biological clock of our cells is extremely complex. We are equipped with security mechanisms that prevent our cells from proliferating in a disorderly fashion.

Some embryonic cells share characteristics similar to those of tumor cells, such as the ability to self-renew and a high rate of proliferation. Thus, reprogramming the security mechanisms of adult cells can lead to unwanted situations, such as the emergence of cancer. An ideal future would be one in which we can turn back the biological clock of our cells in a partial and controlled way, and in which we have techniques to transform and generate new cells in our body, healing injuries and replacing lost limbs.

We are still a long way from this possibility, but recent studies in amphibians have brought encouraging results. Researchers used as a model the frogs of the species Xenopus laevis, which when tadpoles can put together pieces of their tail, but lose their regenerative capacity when they become adults (similar to what happens to us). Frogs that had a leg amputated received dressings with substances to stimulate the growth of the cells that form the leg, and to contain the inflammatory process and the formation of scars. The treatment lasted just one day, and over the next 18 months the amputated limb grew, regenerating muscles, bones, blood vessels and nerves. Although the formed limb was not completely complete, the growth was very significant in relation to the untreated groups, and there was partial recovery of functionality.

Much research with other animal models will still be needed before testing this and other therapies in humans. With the increasing life expectancy of the population, we need to find ways to contain aging and treat loss of limbs or organs caused by trauma and chronic diseases. We do not know when it will be possible to achieve regeneration in humans, but understanding the regenerative mechanisms of hydras and other animals has been fundamental in this process.

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Rossana Soletti is a PhD in morphological sciences and a professor at the Federal University of Rio Grande do Sul.

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