4-Galactosylkojibiose Extends the Lifespan of Drosophila melanogaster.

Oligosaccharides, such as fructooligosaccharides (FOS), have long been used to promote human health due to their beneficial effects on the intestinal environment and their anti-inflammatory properties. Recent advances in manufacturing technologies have enabled the production of novel oligosaccharides derived from rare sugars. These compounds may exert unique health benefits; however, their physiological functions remain largely unexplored. Because sleep is a conserved, lifespan-linked physiological phenotype governed by metabolic and stress-response pathways that oligosaccharides can influence, we evaluated sleep alongside lifespan to capture systemic functional effects. Using the model organism Drosophila melanogaster, we investigated the effects of 4-galactosylkojibiose (4-GK), a promising new oligosaccharide, on sleep and lifespan. We also conducted RNA sequencing following 4-GK or FOS application. Our results demonstrated that both 4-GK and FOS extended lifespan, with 4-GK showing comparable or numerically greater efficacy than FOS. While the addition of 4-GK or FOS to sucrose diet did not affect overall sleep or activity levels, 4-GK alone without sucrose decreased sleep compared to sucrose alone. Furthermore, RNA-seq analysis revealed upregulation of gene groups associated with longevity in both the 4-GK and FOS treatment groups, particularly genes encoding heat shock proteins. 4-GK promotes longevity in D. melanogaster and activates stress-response programs, suggesting a health-promoting role comparable to FOS. Sleep effects were diet-context dependent, unchanged when added to sucrose but reduced when given without sucrose. These findings suggest a novel potential role for 4-GK in promoting longevity.