NUCB1 is required for proper insulin signaling to control longevity in Drosophila

Aim We examined the novel role of NUCB1(Nucleobindin‐1) associated with longevity in Drosophila melanogaster. Methods We measured the lifespan, metabolic phenotypes, and mRNA levels of Drosophila insulin‐like peptides ( Dilps ), the protein level of phosphorylated AKT, and the localization of FOXO and its target gene expressions in the NUCB1 knockdown condition. Results NUCB1 knockdown flies show an extended lifespan and metabolic phenotypes such as increased circulating glucose level and starvation resistance. The mRNA expression levels of Dilps and the protein level of phosphorylated AKT, a downstream component of insulin signaling, were decreased in NUCB1 knockdown flies compared with the control flies. Also, the nuclear localization of FOXO and its target gene expressions, such as d4E‐BP and InR , were elevated. Conclusions The results show that NUCB1 knockdown flies exhibits an extended lifespan. These findings suggest that NUCB1 modulates longevity through insulin signaling in Drosophila . Geriatr Gerontol Int 2024; 24: 486–492 .