Aptamer to Enhance Vitamin C Antioxidant Function Improves Neurovascular Function in Aged Mice

Oxidative stress increases with age, the result of a number of age-related dysfunctions that give rise to excessive levels of oxidative molecules. Increasing levels of commonly available antioxidants does not do any good, however, as illustrated by the failure of supplements such as the antioxidant vitamin C to improve health in anything other than cases of vitamin C deficiency. In the case of vitamin C some of this failure may be due to the fact that vitamin C becomes oxidized and loses its function. Here researchers employ an aptamer that binds to vitamin C to provent oxidation, and show that it improves some measures of function in aged mice by allowing vitamin C to become a much more potent antioxidant.

We have developed Aptamin C320, a DNA aptamer that specifically binds to vitamin C and inhibits its oxidation. Aptamers are single-stranded DNA-based oligonucleotides, and Aptamin C320 inhibits the oxidation of vitamin C and preserves its antioxidant activity in the body. NXP032, a complex of vitamin C and Aptamin C320, effectively removes reactive oxygen species (ROS) and increases antioxidant enzyme activity. It maintains a stable antioxidant effect by inhibiting oxidative stress induced by the activation of the antioxidant response element (ARE) pathway in aged mice.

In this study, we investigated the effect of NXP032 on neurovascular stabilization through the changes of PECAM-1, PDGFR-β, ZO-1, laminin, and glial cells involved in maintaining the integrity of the blood-brain barrier (BBB) in aged mice. NXP032 was orally administered daily for 8 weeks. Compared to young mice and NXP032-treated mice, 20-month-old mice displayed cognitive impairments in Y-maze and passive avoidance tests. NXP032 treatment contributed to reducing the BBB damage by attenuating the fragmentation of microvessels and reducing PDGFR-β, ZO-1, and laminin expression, thereby mitigating astrocytes and microglia activation during normal aging. Based on the results, we suggest that NXP032 reduces vascular aging and may be a novel intervention for aging-induced cognitive impairment.

Link: https://doi.org/10.1038/s41598-023-35833-x