Pitkänen, M.; Matilainen, O.

Milk-derived peptides and milk fat globule membrane (MFGM) have gained interest as health-promoting food ingredients. However, the mechanisms by which these nutraceuticals modulate the function of biological systems often remain unclear. We utilized Caenorhabditis elegans to elucidate how milk-derived Protein powders rich in MFGM, previously used in a clinical trial, affect the physiology of this model organism. Our results demonstrate that Protein powders do not affect lifespan but promote the fitness of the animals. Surprisingly, gene expression analysis revealed that Protein powders decrease the expression of genes functioning on innate immunity, which also translates into reduced survival on pathogenic bacteria. One of the innate immunity-associated genes showing reduced expression upon Protein powder supplementation is cpr-3, the homolog of human cathepsin B. Interestingly, knockdown of cpr-3 enhances fitness, but not in Protein powder-treated animals, suggesting that protein powders contribute to fitness by downregulating the expression of this gene. In summary, this research highlights the value of C. elegans in testing the biological activity of food supplements and nutraceuticals. Furthermore, this study should encourage investigations into whether milk-derived peptides and MFGM mediate their beneficial effects through the modulation of cathepsin B expression in humans.