2023-04-28 07:50:20
Thomas Johnson demonstrated more than three decades ago that modifying a single gene—age-1—increased the lifespan of worms. C. elegans up to 60%. Despite the enormous evolutionary distance that separates us from them, useful mechanisms for survival jump from branch to branch of the tree of life and are conserved in the genomes of many species, including humans. What works on a worm or a mouse, or even on a yeast, need not work on us as well. But the results manipulating the life expectancy of these remote relatives encourages the search for genetic modifications in search of a shorter youth.
Three years ago, a group of researchers from the University of California at San Diego (UCSD) found an essential mechanism in the aging process of a unicellular fungus that has been with us, at least since the origin of civilization. Yeast Saccharomyces cerevisiae, with which bread, beer or wine is made, follows one of two directions on its way to death. Half of these cells age when their DNA loses stability; and the other half, with the deterioration of the mitochondria, a structure that provides energy to the cell. But they don’t go bad both ways at the same time.
The same UCSD researchers, led by Nan Hao, now explain in an article published by the journal Science how they have created a kind of switch that, by manipulating two regulators of gene activity, changes the direction of cell aging. From DNA to mitochondria decay and back again, that mechanism keeps brewer’s yeast cells in a balance between their pathways to sunset. In a way similar to a thermostat, where when a higher temperature is reached the refrigerator is turned on and when a lower limit is reached heat is introduced, here synthetic biology is applied to introduce a similar system. With what is known as a genetic oscillator, cells change the way they age when they have gone too far in one of two directions. With this game of balances, they have prolonged their existence by up to 80%, a new world record in biology, and the researchers suggest that this type of oscillators could serve to slow down the path to death that begins every time a cell appears. Also those of the human body.
slow down aging
Now the authors intend to “identify the regulatory genetic circuits underlying aging in various types of human cells and apply this engineering strategy to modify them and slow down their aging,” explains Nan Hao, lead author of the study and co-director of the Institute of Synthetic Biology of the UCSD. “If it works, we’ll try to do the same thing in cells inside living animals, like mice,” he adds. Hao acknowledges that genetic engineering “requires more time in human cells, and the circuitry that regulates genes is often more complicated,” he continues. “We will need more time and resources to test these ideas and strategies, but I don’t think there is anything fundamental that prevents us from doing it,” he concludes.
Carlos López Otín, a researcher at the University of Oviedo and an expert in aging, recognizes the value of the study by these researchers who, like others before them, have used “simple models to try to understand the colossal and fascinating complexity of life.” “It may seem strange that from a single-celled organism we can learn lessons about the effect of time on our bodies made up of many trillions of cells of more than 200 different types. But, we must not forget a mythical phrase from the great Jacques Monod, Nobel Prize in Medicine for discovering the first keys to gene regulation in bacteria: ‘What is valid for a bacterium is also valid for an elephant,’ he continues. “However,” he questions, “its extrapolation to human cells and our daily lives still seems far away.”
“Unicellular organisms [como la levadura empleada en este experimento] they are naturally selfish, their main objective is to divide: the dream of a bacterium or a yeast is to create others just like them”, explains López Otín. This “cellular egoism is a purpose that our altruistic and supportive cells reject” and only adopt it if, by accumulating molecular damage, they transform and become tumorous. “For this reason, in humans it is not enough to prevent cells from aging at all costs and to extend longevity. The price of these strategies so publicized and longed for by some can be the development of serious pathologies, including malignant tumors, capable of reducing human longevity considerably”, continues López Otín.
For the scientist, the question that arises from these results is: if evolution could have created an oscillator similar to the one created by these authors by modifying only two genes, why hasn’t this happened since the appearance of life more than 3,500 million years ago? years? In order to understand the reason for this lack and understand the costs of extending longevity, López Otín proposes carrying out an experiment in which yeasts carrying the modified genes are allowed to compete with the corresponding normal yeasts “to analyze if any of the strains imposes selectively over time under different conditions. In addition, he proposes creating other types of oscillators, not to unnecessarily extend longevity, but in an effort to maintain homeostasis, our essential internal balance. “This could contribute to improving our health, something that seems to me a more sensible and affordable goal than aspiring to improbable dreams of immortality,” he concludes.
For Jordi García Ojalvo, a researcher at the Universitat Pompeu Fabra in Barcelona and a collaborator with Michael Elowitz, creator of the first synthetic genetic oscillator, he believes that “beyond the applications that the results of this study may have, which could arrive within many years, the most interesting thing is that it shows how synthetic biology can be used to understand how organisms work and how they age, it helps us push the limits of that knowledge”. “Aging in human cells or in a whole organism is very complicated, but all cells on Earth have 20 amino acids and the same four nucleic acids,” he adds. “What we learn from these cells, as well as being very interesting, could be useful to look for applications many years later,” he sums up.
You can follow THE COUNTRY Health and Well-being in Facebook, Twitter e Instagram.
#keys #extending #life #hidden #microbe #beer #wine #Health #Wellness