Age and Dietary Vitamin C Intake Affect Brain Physiology in Genetically Modified Mice Expressing Human Lipoprotein(A) and Unable to Synthesize Vitamin C

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Shi L, Niedzwiecki A, Rath M.

Current Aging Science 2021; 14(3).



Aims: Lipoprotein (a) deposition in coronary vascular plaques and cerebral vessels is a recognized risk factor for cardiovascular disease, and research supports its role as a “repair factor” in vascular walls weakened by vitamin C deficiency.

Background: Humans depend on dietary vitamin C as an important antioxidant and as a cofactor in collagen synthesis, yet are prone to vitamin C deficiency. The brain is the one with the highest vitamin C content, owing to its high oxygen consumption and oxidative stress. It has been shown that brain aging is accompanied by accumulated oxidative damage, which can lead to memory decline and neurological diseases.

Objective: Our transgenic mouse, Gulo (-/-); Lp(a)+, presents a unique model for the study of key aspects of human metabolism with respect to a lack of internal vitamin C synthesis and the production of human lipoprotein(a).

Methods: This mouse model was used in our study to investigate the effects of prolonged intake of low and high levels of vitamin C, at different ages, on oxidative damage, cholesterol levels and lipoprotein(a) deposition in the brain.

Result: The results show that a long-term high vitamin C intake is important in maintaining brain cholesterol homeostasis and preventing oxidative damage in Gulo(-/-);Lp(a)+ mice as they age. Moreover, we observed that the formation of brain lipoprotein(a) deposits was negatively correlated with brain level of vitamin C, thereby confirming its role as a stability factor for an impaired extracellular matrix.

Conclusion: Our study emphasizes the critical role of vitamin C in protecting brain health as we age. Our findings show that optimal vitamin C intake from early life to old age is important for brain health as it prevents oxidative stress damage and maintains cholesterol homeostasis in the brain. More importantly, the negative correlation between brain ascorbic levels and the formation of Lp(a) deposit on the choroid plexus further emphasizes the critical role of vitamin C in protecting brain health throughout the normal aging process.


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