Casein Hydrolysate Peptides Attenuate Immunosenescence and Inflammaging in a D-Galactose-Induced Mouse Model of Aging

Aging populations worldwide face increasing burdens from physiological deterioration. Bioactive peptides derived from milk proteins have attracted interest for their biological activities, yet systematic evidence against aging remains limited. Here, we investigated casein hydrolysates in a D-galactose-induced murine aging model. Following eight weeks of oral administration at graded doses, we quantified systemic oxidative stress markers, inflammatory cytokine profiles, hepatic and cerebral histopathology, and multiple immune competence parameters. Our data demonstrate that casein peptides dose-dependently suppressed lipid peroxidation, elevated endogenous antioxidant enzyme activities, and rebalanced cytokine networks toward an anti-inflammatory state. Concurrently, peptide treatment attenuated tissue lesions in both liver and brain, while restoring thymus and spleen indices, normalizing T-cell subset distributions, and recovering serum immunoglobulin levels. These findings indicate that oral administration of the casein hydrolysate peptide preparation was associated with improvements in redox homeostasis, inflammatory status, tissue integrity, and immune function in D-galactose-induced aging mice. This work provides mechanistic insights into casein peptides as a multi-target protective agent against age-associated physiological decline, supporting further exploration of their therapeutic potential in aging biology.