BUFFALO, NY — December 12, 2025 — A groundbreaking study has revealed that a natural compound can effectively reverse arterial stiffening in mice, a condition often linked to aging and metabolic disorders such as diabetes. Published in the latest issue of Aging-US, the research highlights the potential of glycation stress-lowering compounds in mitigating cardiovascular risks.
The study, conducted by researchers from the Buck Institute for Research on Aging and the University of Colorado Boulder, delves into the effects of methylglyoxal (MGO), a toxic byproduct that accumulates in blood vessels over time. This buildup is associated with increased arterial stiffness, a significant predictor of cardiovascular disease in older adults.
Understanding Arterial Stiffening and Glycation Stress
Aortic stiffening reduces the flexibility of the body’s largest artery, compromising cardiovascular health. The research team, led by Parminder Singh and Ravinandan Venkatasubramanian, used both young and aged mice to explore the impact of MGO on vascular health. Their findings revealed that chronic exposure to MGO increased aortic stiffness by 21% in young mice.
However, the introduction of Gly-Low, a supplement containing natural compounds such as nicotinamide and alpha-lipoic acid, completely prevented this stiffening. Gly-Low not only reduced the accumulation of MGO but also its harmful byproducts, particularly MGH-1, in both blood and tissue samples.
Mechanisms of Action
The study’s results extend beyond structural changes in the arteries. MGO was found to induce senescence in endothelial cells, the cells lining blood vessels, causing them to cease division and release inflammatory signals. This process led to decreased levels of nitric oxide, a crucial molecule for blood vessel relaxation.
In laboratory cultures of human vascular cells, Gly-Low reversed these aging-like changes and restored nitric oxide production, suggesting its potential therapeutic benefits.
Implications for Aging and Diabetes
In older mice, which naturally develop stiffer arteries, Gly-Low treatment over four months significantly reduced stiffness and lowered levels of MGO and MGH-1. This indicates that Gly-Low might slow or even reverse vascular aging by reducing glycation stress.
The study also identified the glyoxalase-1 pathway as a critical mechanism. This natural detoxification system helps clear harmful molecules like MGO. Gly-Low appeared to enhance this pathway, and when it was chemically blocked, Gly-Low’s protective effects vanished, confirming its role in the process.
Expert Opinions and Future Directions
According to Pankaj Kapahi, one of the senior authors, “These findings highlight glycation stress as a modifiable contributor to vascular aging. The potential for natural compound-based therapies, like Gly-Low, to protect arteries from age- and diabetes-related damage is significant.”
“Aortic stiffness was assessed in vivo via pulse wave velocity (PWV) and ex vivo through elastic modulus.”
The research underscores the importance of addressing glycation stress in the context of aging and metabolic diseases. With cardiovascular diseases remaining a leading cause of mortality worldwide, innovations in treatment strategies are crucial.
Looking Ahead
The implications of this study are vast, offering a potential new avenue for therapeutic intervention in age-related cardiovascular conditions. While the research is still in its early stages, the promising results in animal models pave the way for future studies in humans.
As the global population continues to age, the demand for effective treatments to combat age-related diseases will only increase. The findings from this study could inform future clinical trials and potentially lead to new, non-invasive treatments for cardiovascular health.
For more detailed information, the full paper is accessible at https://doi.org/10.18632/aging.206335.
