A A genetic adjustment that improves the precision of protein synthesis can lengthen the lifespan of an organism, according to an article published this week (September 14) in Cell metabolism. The results were consistent in three species — the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and yeast Schizosaccharomyces pombe– suggesting that building better proteins may also be linked to longevity in other species.
“The work is very compelling, very compelling, and I think it answers a really important open question in aging: what are the best ways to take care of our proteins and help us function better for longer. ? Said protein researcher John Labbadia from University College London who was not involved in the research.
As an organism ages, the efficiency and accuracy of its cellular processes deteriorate. For example, protein production, folding and degradation all decline in quality, so the loss of protein homeostasis (proteostasis) is “a major feature of aging” and age-related diseases, explains molecular biologist Patricija van Oosten-Hawle from the University. from Leeds who did not participate in the search.
In the case of protein production – the translation of the RNA code into peptide chains – the prevalence of errors “correlates positively with lifespan,” writes Vera Gorbunova, University of Rochester aging researcher, who was not on the research team, wrote in an email to The scientist. However, “evidence showing that one can take a short-lived organism and extend its lifespan by making the translation more precise was lacking,” she writes, adding that the new Cell metabolism paper “provides this last missing proof”.
In the cell’s protein factories, called ribosomes, a protein called RPS23 is considered essential for translational accuracy. RPS23 was therefore the obvious candidate to look for ways to improve fidelity, explains molecular biologist Ivana Bjedov of the Cancer Institute at University College London. His team has studied RPS23 in species ranging from mammals to microbes. Within the protein, they found a region so highly conserved that, with the exception of some microorganisms that live in extremely hot environments, all species had an identical amino acid at the same position.
What are the best ways to take care of our protein and help us function better, longer?
—John Labbadia, University College London
Bjedov wondered how the single amino acid change seen in thermophiles might affect the accuracy of translation. His team introduced the change in the RPS23 gene of D. melanogaster and found that not only was the accuracy of the translation improved, but the flies could also survive higher temperatures and lived about 10-20% longer than control flies.
Bjedov’s collaborator Filipe Cabreiro of the MRC London Institute of Medical Science then introduced the same RPS23 amino acid change in C. elegans and obtained similar results. Other studies have shown that the amino acid change also increases the accuracy of translation and the lifespan of the yeast.
Finding consistent results on three species “makes you more reassured about what you see,” says Cabreiro. “It’s a robust observation.”
In flies and worms, the life-prolonging mutation was associated with delayed development and reproduction, although ultimately the number of offspring produced was similar to that of control animals. Likewise, in yeast, the mutation resulted in slower colony growth. It is not known why the mutation caused this developmental delay. Translation rates between test and control animals appeared to be equivalent, as were other phenotypic traits. But the delay could explain why the mutation – which is otherwise apparently beneficial – is not more prevalent in nature, the researchers say.
Finally, the team showed that, for the flies at least, the animals not only had extended lives, but extended health – geriatric test flies could still be seen climbing the sides of their vials when the Control flies of similar age no longer did. Essentially, the test flies stayed young longer.
An important next step for this research, says van Oosten-Hawle, would be “to examine what would happen in model vertebrate systems.” . . how this [mutation] would affect longevity in mice, for example. If such experiments show results similar to flies, worms and yeasts, the ultimate question, Labbadia says, would be, “How do we get this to humans?” “