bioRxiv · Oct 28, 2026
A novel function of neuroligin 3: Beyond sociality, Regulating lifespan in Drosophila
By Jurbaj JM, Ataei R, Simon AF
Neuroligins are conserved postsynaptic adhesion proteins involved in synaptic function and behaviour. In Drosophila melanogaster, Neuroligin 3 (Nlg3) regulates social behaviour, sleep and synaptic architecture. We now report, through analysis of publicly available transcriptomics data, confirmed with RT-qPCR data, that loss-of-function of the nlg3 gene downregulates the expression of longevity-associated genes foxo, hsp70s, and hsp68. Graded genetic manipulation of the Drosophila melanogaster neuroligin 3 (nlg3) gene indeed modulates both social spacing and lifespan. Specifically, reduced nlg3 expression (via heterozygous deletion, or transposable-element insertion) extends lifespan in both sexes, while overexpression or complete deletion shortens it. In contrast, overexpression or complete loss of nlg3 leads the flies to be further apart (increased social distance, or social space), as does RNAi knockdown, while heterozygous reduction of nlg3 expression either lowers or does not alter the flies social space. This work identifies a previously unrecognized link between a conserved synaptic gene, social behaviour, and organismal longevity.