Dietary restriction extended the lives of flies further when researchers silenced nine ancient genes
Dietary restriction extended the lives of flies further when researchers silenced nine ancient genes
On 16 July, EMBO Reports published a study of eight Drosophila species. The authors identified a shared response to dietary restriction, selected 15 evolutionarily ancient genes, and temporarily silenced them in adult flies. Nine of these interventions increased lifespan on the restricted diet.
In fly experiments, dietary restriction consists of a series of diets containing different proportions of yeast, the main protein source. A team from the University of Sheffield gave eight Drosophila species five such diets. Five species lived longer on less nutrient-rich food, although the optimal proportion of yeast differed between species. Egg production also declined in flies receiving the diet that maximized lifespan.
The researchers then examined which genes changed their activity under these dietary conditions. In six species, they compared 6 926 shared genes. The responses tended to move in the same direction: the same groups of genes were more likely to become more or less active together across different species. However, most of the most responsive genes emerged relatively recently in evolution and are found mainly in arthropods.
A shared RNA signature does not by itself demonstrate a shared mechanism of longevity. This signature combines ancient processes with adaptations that each species developed in response to food scarcity. The authors selected 15 genes that changed their activity consistently across species and were already present in distant animal ancestors. They temporarily silenced each gene using RNA interference, a method that causes cells to degrade RNA from the selected gene and reduces production of the corresponding protein.
Lifespan changed after 12 of the interventions. Nine increased the effect of the restricted diet. Five of these nine genes normally became more active during dietary restriction, yet silencing them produced a further increase in lifespan. The authors propose that part of the response to food scarcity protects current physiological function. Cells attempt to conserve and redistribute scarce substances, and this compensatory response may partly reduce the extension of lifespan.
Genes involved in the metabolism of the sulfur-containing amino acids cysteine, methionine, and serine were especially common among the selected candidates. These molecules contribute to protein synthesis, antioxidant defense, and one-carbon metabolism. The findings provide a direction for the next round of experiments: determining which compensatory responses limit the effect of the diet and whether they can be targeted more precisely.
A review of how tissues and feedback mechanisms weaken individual anti-aging interventions examined this problem in complex organisms. The new study presents a possible specific example in flies. The organism activates its own responses to food scarcity, and some of these responses reduce the resulting gain in longevity.
The study covers adult female flies and diets containing different proportions of yeast. Applying these findings to humans will require testing the targets in mammals and assessing their safety separately. For now, the most valuable result is a method for finding a shared mechanism within a vast list of genes whose activity has changed: compare species, select ancient candidates, and immediately test whether altering them changes animal lifespan.