Genotype and Sex Specific Effects of Methionine Restriction on the Life and Healthspan of Drosophila melanogaster

Abstract

Reduced dietary intake of the amino acid methionine has been reported to significantly extend the lifespan of common laboratory model organisms including Saccharomyces cerevisiae, Mus musculus, and Drosophila melanogaster. Methionine restriction (MR) has also been achieved via non-dietary means such as metabolite supplementation and CRISPR-Cas9 gene editing. MR along with protein and calorie restriction are known as dietary interventions capable of producing pro-longevity benefits through regulation of nutrient sensing pathways. Recent studies in model organisms have also identified beneficial effects of a low methionine diet on aging-associated phenotypes and markers of overall healthspan. However, the effects of this intervention on genetically diverse populations have yet to be explored.

In this study, we investigate the relationship between sex and genetic factors on determining the outcomes of a long-term MR diet given to multiple strains of the fruit fly D. melanogaster. We found significant variation in the survival response, including lifespan shortening in addition to previously reported lifespan extension. Additionally, we report an observed lack of correlation between resistance to oxidative stress and pro-longevity benefits. These results suggest a significant genetic component to the longevity phenotype of MR as well as context-dependent mechanisms involved in its regulation.