4-Galactosylkojibiose Extends the Lifespan of Drosophila melanogaster

BACKGROUND/OBJECTIVES: 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. METHODS: , 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. RESULTS: 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. CONCLUSIONS: 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.