Egg Peptides From American Shad Extend Lifespan and Healthspan in Caenorhabditis elegans via Lipid Metabolism Remodeling and Antioxidant Defense

Abstract

Given the increasing focus on natural interventions for healthy aging, this research evaluates the longevity‐promoting potential of egg‐derived peptides (EPs) extracted from American shad (Alosa sapidissima). Using Caenorhabditis elegans as the experimental model, researchers found that 0.15 mg/mL EP supplementation extended lifespan by a remarkable 33.33%. EP also significantly enhanced healthspan, improving physiological metrics such as head thrashing, body bending, and pharyngeal pumping by 24.37%, 22.33%, and 28.81%, respectively. Furthermore, EP reduced aging biomarkers—including lipofuscin and reactive oxygen species (ROS)—by up to 40.34%, while boosting overall antioxidant capacity (SOD increased by 53%, MDA decreased by 30.76%). Transcriptomic analysis identified 2196 differentially expressed genes (DEGs) out of 23 057 total identified genes, providing deep insights into the mechanisms underlying EP‐mediated longevity. Crucially, EP upregulated genes responsible for unsaturated fatty acid biosynthesis (fat‐7 and elo‐4) to optimize cell membrane fluidity. Conversely, it downregulated genes linked to fatty acid β‐oxidation (acs‐2, acox‐1.5, ech‐9, hacd‐1) and endogenous stress responses (sod‐3, hsp‐16.1, hsf‐1). Validated via qRT‐PCR, these shifts indicate that EP extends lifespan by fundamentally remodeling lipid metabolism and maintaining redox homeostasis. Ultimately, these findings highlight EP as a highly promising functional food ingredient for promoting healthy aging.