Globally, over 5 billion people are affected by retinal degenerative diseases and blindness—most of these visual impairments result from age-related cellular senescence. Retinal diseases remain a major unmet medical challenge.
Grape seed extract contains proanthocyanidins (a compound with strong antioxidant properties). Proanthocyanidins are most abundant in grape seeds and have been used clinically in Europe for decades, with effects including improving blood circulation, treating diabetic retinopathy, reducing edema, and inhibiting varicose veins. They also have multiple roles in skincare (anti-aging, UV/radiation resistance, brightening, moisturizing) and counteract skin aging caused by various factors.
When heated in an acidic medium, proanthocyanidins produce anthocyanins (a source of plant color with mild antioxidant effects, often used as a colorant in cosmetics).
Key Study Findings
Researchers from The First Affiliated Hospital of Zhengzhou University demonstrated that grape seed proanthocyanidin extract (GSPE) alleviates retinal cell senescence in aged mice by boosting NMN and NAD+ levels.
1. Proanthocyanidins Delay Retinal Cell Senescence
The retinal pigment epithelium (RPE)—the outer layer of the retina—nourishes retinal visual cells. RPE dysfunction is a key driver of multiple degenerative eye diseases.
GSPE has antioxidant, anti-inflammatory, and anti-aging properties, and was shown to increase levels of NAMPT (nicotinamide phosphoribosyltransferase). In retinal degenerative diseases, NAMPT expression and NAD+ content are significantly lower in senescent cells than in healthy cells.
GSPE delays retinal cell senescence by:
- Increasing NAMPT levels → boosting NMN production → elevating NAD+ content.
Figure Note 1: Diagram of NAMPT-NMN-NAD+ conversion (NAM = nicotinamide; NR = nicotinamide riboside; NMNAT1-3 = NMN adenylyltransferases 1–3).
Figure Note 2: Proanthocyanidins (GSPE) protect retinal cells in mice (comparisons: Normal group vs. Aging group vs. Aging + GSPE group; ***P<0.001).
2. Correlation Between Proanthocyanidins and NMN
To confirm the link between proanthocyanidins and NMN, researchers used an inhibitor (FK866) to block NAMPT activity:
- Blocking NAMPT → reduced NMN levels → accelerated cellular senescence.
- Stimulating cells with GSPE → restored NAMPT activity → significantly increased NMN levels → reversed senescence and protected cells.
- Additionally, supplementing NMN alongside GSPE (after NAMPT inhibition) also restored the anti-senescence effect.
Figure Note: Proanthocyanidins regulate NAD+ levels in senescent cells (comparisons: Normal group vs. Aging group vs. Aging + GSPE group vs. Aging + GSPE + FK866 group vs. Aging + GSPE + FK866 + NMN group; ***P<0.001).
3. NMN and NAMPT: Implications for Anti-Aging
The study highlights that natural substances (like grape seed proanthocyanidins) hold potential for health improvement. While numerous studies confirm NAD+’s anti-aging effects, multiple strategies exist to boost NAD+ (e.g., direct NMN supplementation vs. NAMPT activators). More clinical research is needed to determine the optimal approach, but these strategies all offer avenues to improve health and lifespan.
References
Wan, W., Zhu, W., Wu, Y., Long, Y., Liu, H., Wan, W., Wan, G., Yu, J. (2021). Grape Seed Proanthocyanidin Extract Moderated Retinal Pigment Epithelium Cellular Senescence Through NAMPT/SIRT1/NLRP3 Pathway. Journal of Inflammation Research, 14, 3129–3143. https://doi.org/10.2147/JIR.S306456