# The Antioxidant and Antiaging Properties of Maillard Reaction Products Derived From Dipeptide Lys–Leu in Caenorhabditis elegans

## TL;DR

This study shows that Maillard reaction products from the dipeptide Lys–Leu have strong antioxidant effects and can extend the lifespan of the worm C. elegans.

## Contribution

The novel finding is that Lys–Leu MRPs extend lifespan and healthspan in C. elegans via antioxidant activity and the insulin/insulin-like growth factor signaling pathway.

## Key findings

- Lys–Leu MRPs after 2 h heat treatment showed highest antioxidant activity in vitro.
- Lys–Leu MRPs extended lifespan and improved motility in C. elegans under normal and oxidative stress.
- Lifespan extension by Lys–Leu MRPs was blocked in sod-3 and daf-16 mutants, indicating IIS pathway involvement.

## Abstract

The Maillard reaction, a nonenzymatic browning reaction that occurs between amines and carbonyl groups during food processing and cooking, generates products with antioxidant activity. Dipeptides composed of leucine and lysine (Leu–Lys and Lys–Leu) are frequent sequences in a variety of food proteins. Previously, we demonstrated that these dipeptides exhibit antioxidant activity and extend the lifespan of the nematode
Caenorhabditis elegans
(
C. elegans
). Although the Maillard reaction can improve peptide bioactivity, its effects on Leu–Lys and Lys–Leu remain unclear. Therefore, we investigated the antioxidant activity of Maillard reaction products (MRPs) derived from these dipeptides in vitro and their effects on the aging process in
C. elegans
. The antioxidant activity of Leu–Lys was unaffected by the Maillard reaction. By contrast, MRPs generated from Lys–Leu exhibited the highest antioxidant activity after 2 h of heat treatment with glucose. In wild‐type
C. elegans
, the administration of Lys–Leu MRPs extended lifespan under both normal and oxidative stress conditions and improved motility with aging. In addition, Lys–Leu MRPs reduced the accumulation of reactive oxygen species and increased the mRNA expression of an antioxidant‐related gene (sod‐3). However, lifespan extension by Lys–Leu MRPs was not observed in sod‐3 and daf‐16 mutants. These findings suggest that Lys–Leu MRPs extend the lifespan of
C. elegans
via the insulin/insulin‐like growth factor signaling pathway.

Lys–Leu MRPs heat‐treated for 2 h exhibited high antioxidant activity in vitro. A treatment with Lys–Leu MRPs extends the lifespan and health span of
C. elegans
by regulating ROS levels through their inherent antioxidant activity and the IIS pathway.