The key to longevity could be hidden in the microorganisms used to make beer and wine. An experiment has succeeded in increasing the lifespan of a species of yeast by 80% using synthetic biology techniques.
A simple gene modified to live longer
More than three decades ago, Thomas Johnson showed that modifying a single gene – called age-1 – could increase the lifespan of C. elegans worms by 60%. Despite the enormous evolutionary distance between us and these creatures, certain survival mechanisms are conserved in the genomes of many species, including humans. What works on a worm, a mouse or even a species of yeast might not work on us, but the results obtained by manipulating the life expectancy of these close relatives encourage the search for genetic modifications.
The secret of longevity in a thousand-year-old yeast
Three years ago, a group of researchers at the University of California, San Diego (UCSD) discovered a key mechanism in the aging process of a single-celled fungus that has accompanied us since the beginning of civilization. The yeast species Saccharomyces cerevisiae, used to make bread, beer and wine, follows one of two paths to death. Half of its cells age when their DNA loses stability, while the other half age with the deterioration of the mitochondria, a structure providing energy to the cell.
Genetic manipulation to reverse cellular aging
The same UCSD researchers, led by Nan Hao, published a paper in the journal Science explaining how they created a kind of switch that, by manipulating two regulators of gene activity, reverses cellular aging. Thanks to a mechanism called “genetic oscillator”, cells change their aging mode when they have progressed too far in one of the two directions. With this balancing act, scientists have extended the existence of yeast by 80% – a new world record in biology. The researchers suggest that this type of oscillator could also serve to slow the path to death that begins each time a cell appears in the human body.
Application of this strategy to human cells
The authors intend to “identify the genetic regulatory circuits [sous-jacents] of aging in various types of human cells and apply this engineering strategy to modify them and slow down their aging,” says Nan Hao, lead author of the study and co-director of UCSD's Institute for Synthetic Biology. “If it works, we will try to do the same thing in cells inside living animals, such as mice,” he adds.
Nan Hao acknowledges that genetic engineering “requires more time in human cells and the circuits that regulate genes are often more complicated. 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.
Understanding the complexity of aging
Carlos López Otín, a researcher at the University of Oviedo (Spain) and an expert in aging, recognizes the value of the study conducted 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 about the effect of time on our bodies composed of many trillions of cells. But let us not forget the legendary phrase of the great Jacques Monod (Nobel Prize in Medicine) for having discovered the first keys to gene regulation in bacteria: “What is valid for a bacterium is also valid for an elephant.” However, its extrapolation to human cells and to our daily lives still seems remote.”
Improving our health rather than seeking immortality
Carlos López Otín explains that single-cell organisms [comme la levure utilisée dans cette expérience] are naturally selfish: their main objective is to divide. However, in the case of humans, it is not enough to prevent cells from aging at all costs and to extend longevity. The cost of such strategies may be the development of serious pathologies, including malignant tumors, capable of significantly reducing human longevity.
For López Otín, 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 has this not happened since life appeared more than 3.5 billion years ago?
To understand this shortcoming and the costs associated with extending longevity, López Otín proposes to conduct an experiment in which yeast carrying the modified genes are allowed to compete with the corresponding normal yeast. In addition, he proposes to create other types of oscillators, not to unnecessarily extend longevity, but to maintain homeostasis, our essential internal balance. “This could help improve our health…which seems like a more sensible and affordable goal than aiming for improbable dreams of immortality,” he concludes.
For Jordi García Ojalvo, a researcher at the Universitat Pompeu Fabra in Barcelona and collaborator of Michael Elowitz, creator of the first synthetic genetic oscillator, he believes that “beyond the applications that the results of this study could have [dans de nombreuses années]the interesting aspect is that it shows how synthetic biology can be used to understand the functioning of organisms and their aging. It helps us push the boundaries of that knowledge.”
“Aging in human cells or in a whole organism is very complicated. But every cell on Earth has 20 amino acids and the same four nucleic acids,” he adds. “What we learn from these cells can be useful in looking for applications.”
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