Maternal age modulates progeny social behavior via a small RNA–neuropeptide axis

ABSTRACT Parental age influences offspring traits across species, yet the molecular pathways by which maternal state modulates progeny neural function remain poorly defined. Here we demonstrate that maternal age in C. elegans regulates progeny avoidance of the social pheromone by modulating the activity of a defined sensory circuit. Progeny of young mothers exhibit stronger activity of the pheromone-sensing ADL neurons and enhanced pheromone avoidance, whereas progeny of old mothers display reduced neuronal responses and weaker repulsion. We identify an ERI-1–microRNA–neuropeptide signaling axis operating in peptidergic AVH interneurons that modulates ADL circuit responsiveness. ERI-1 promotes expression of the neuropeptide gene flp-26 by repressing mir-8207, and signaling from AVH to ADL establishes pheromone sensitivity. Maternal aging is associated with reduced ERI-1 expression in progeny AVH neurons and dampening this signaling pathway. Consequently, progeny of young mothers, though developmentally less robust, disperse more readily from crowded, pheromone-rich environments, offsetting their early-life disadvantages. Our findings reveal a molecular and circuit-level mechanism by which maternal physiology adaptively configures offspring neural computation and behavioral strategy across generations. Competing Interest Statement The authors have declared no competing interest.