Phosphatidylserine modulates response to oxidative stress through hormesis and increases lifespan via DAF-16 in Caenorhabditis elegans

Phosphatidylserine is one of the phospholipids present in cell membranes, especially in brain and nervous system. The phosphatidylserine content is reduced with aging and age-related decrease in phosphatidylserine is known to contribute to cognitive impairment and Alzheimer’s disease in the elderly. In the present study, we examined the effect of supplementation with phosphatidylserine on the response to oxidative stress and aging using C. elegans as a model system. Dietary supplementation with phosphatidylserine significantly increased resistance to oxidative stress and extended lifespan accompanying reduced fertility as a trade-off. Age-related decline in motility was also delayed by supplementation with phosphatidylserine. The cellular levels of reactive oxygen species and the expression of stress-responsive genes were increased by phosphatidylserine treatment, suggesting a hormetic effect. The extension of lifespan by phosphatidylserine overlaps with reduced insulin/IGF-1-like signaling and requires DAF-16. The effect of phosphatidylserine on age-related diseases was examined using animal model of disease. Supplementation with phosphatidylserine significantly suppressed amyloid beta-induced toxicity in Alzheimer’s disease model. Reduced survival in diabetes mellitus due to high-glucose diet was reversed by supplementation with phosphatidylserine. This study reports the anti-oxidative stress and anti-aging effect of phosphatidylserine for the first time at the organismal level and proposes possible underlying mechanisms.