Identification and molecular mechanism of tilapia skin-derived collagen peptides mitigating aging using zebrafish aging model

Tilapia skin collagen peptides possess multiple biological functions, yet their potential value remains underdeveloped and underutilized. This study investigated the efficacy and mechanisms of tilapia skin collagen peptides (TSCPs) in mitigating aging. TSCPs significantly delayed aging progression in H 2 O 2 - and glucose-induced zebrafish models. Three tyrosinase-inhibitory peptides and five antiglycation peptides were identified in TSCPs through targeted screening. Specifically, peptides Ser-Glu-Gly-Lys (SEGK) and Asp-Asp-Asp (DDD) exhibited the strongest in vitro tyrosinase-inhibitory and antiglycation activity, respectively. Molecular dynamics simulations revealed that both peptides bound more stably to anti-aging targets (tyrosinase and receptor for advanced glycation end products (RAGE)) through hydrogen bonds and electrostatic interactions. Moreover, SEGK and DDD reduced reactive oxygen species (ROS), malondialdehyde (MDA), and advanced glycation end products (AGEs) levels in zebrafish models, thereby contributing to the preferable aging mitigation effects. These findings provide in-depth insights into the mechanisms by which TSCPs mitigate aging from the perspectives of antioxidation, antiglycation, and tyrosinase inhibition, offering a theoretical basis for the development of TSCPs-based functional foods.