Sea cucumber (Acaudina leucoprocta) peptides exhibit anti-aging effect in Drosophila melanogaster via regulation of microbiota dysbiosis and metabolic disorder

As the population ages, the pursuit of extended lifespan and improved healthspan has gained significance. This study assessed the anti-aging properties of sea cucumber peptides derived from Acaudina leucoprocta (SCP) through microbiome and metabolome analyses in Drosophila melanogaster. Supplementation with 0.2%, 0.4%, 0.6%, and 0.8% of SCP significantly boosted the survival rate and extended the mean and median lifespans in both male and female flies. Among them, 0.6% SCP treatment extended the mean and median lifespans of male flies by 21.01% and 25.48 %, which showed the most prominent lifespan-prolonging effect. Moreover, SCP enhanced the healthspan of male flies by improving their climbing ability, intestinal barrier function, and memory performance. Additionally, SCP boosted the survival rate of flies subjected to oxidative, starvation, and heat stress, with no significant effect observed under cold stress conditions. The lifespan-extension effect of SCP remained unaffected by dietary restriction, but was partially inhibited when provided with antibiotic-supplemented food. SCP modulated microbiota with increased the abundance of Lactobacillus, Rhodococcus, and Propioniciclava and decreased Acetobacter, Achromobacter, Pedobacter, and norank_f_Saprospiraceae, which closely related with lifespan-extension effect. Furthermore, SCP induced a metabolic profile in 30-day-old flies more akin to that of 3-day-old flies, impacted 13 significantly regulated metabolites associated with amino acid, nucleotide, and carbohydrate metabolisms. These findings highlight SCP intervention as a promising anti-aging strategy.