Alterations in brain glycogen levels influence life-history traits and reduce the lifespan in female Drosophila melanogaster

Sexual dimorphism in lifespan, wherein females outlive males, is evident across all animal taxa. The longevity difference between sexes is controlled by multiple physiological processes with complex relationships to one another. In recent years, glycogen, the storage form of glucose, has been shown to cause rapid aging upon forced synthesis in healthy neurons. Glycogen in the form of corpora amylacea in the aging brain is also widely reported. While these studies did suggest a novel role for glycogen in aging, most of them have focused on pooled samples, and have not looked at sex-specific effects, if any. Given the widespread occurrence of sex-biased expression of genes and the underlying physiology, it is important to look at the sex-specific effects of metabolic processes. In the present study, using transgenic fly lines for the human glycogen synthase, we investigated the sex-specific effects of glycogen on stress resistance, fitness, and survival. We demonstrate that Drosophila melanogaster females with altered levels of glycogen in the brain display a shortened lifespan, increased resistance to starvation, and higher oxidative stress than male flies. The present study thus provides a novel insight into the sex-specific effect of glycogen in survival and aging and how differences in metabolic processes could contribute to sex-specific traits.