BUFFALO, NY — December 12, 2025 — A groundbreaking study published in the journal Aging-US has shed light on a potential therapeutic approach to combat arterial stiffening, a significant risk factor for cardiovascular disease. The research, led by scientists from the Buck Institute for Research on Aging and the University of Colorado Boulder, focuses on the role of methylglyoxal (MGO), a toxic byproduct that accumulates in the blood vessels as a result of aging and metabolic disorders like diabetes.
The study, titled “Methylglyoxal-induced glycation stress promotes aortic stiffening: putative mechanistic roles of oxidative stress and cellular senescence,” was published in Volume 17, Issue 11 of the journal on November 14, 2025. It highlights the potential of a natural compound-based supplement, Gly-Low, in preventing and reversing the stiffening of arteries in mice.
Understanding Aortic Stiffening and Glycation Stress
Aortic stiffening is a condition where the body’s largest artery loses its flexibility, increasing the risk of cardiovascular disease, especially in older adults. The research team, including first authors Parminder Singh and Ravinandan Venkatasubramanian, explored how MGO contributes to this condition. Their findings are particularly relevant for individuals with diabetes, who are at an increased risk of cardiovascular complications.
Using both young and aged mice, the researchers discovered that chronic exposure to MGO increased aortic stiffness by 21% in young mice. However, treatment with Gly-Low, which contains natural compounds such as nicotinamide and alpha-lipoic acid, completely prevented this stiffening. The supplement also effectively reduced the accumulation of MGO and its harmful byproducts, particularly MGH-1, in blood and tissue samples.
The Role of Gly-Low in Vascular Health
The study revealed that MGO’s detrimental effects extend beyond structural changes in the arteries. It induces cellular senescence in endothelial cells, leading to reduced levels of nitric oxide, a molecule crucial for blood vessel relaxation. In laboratory cultures of human vascular cells, Gly-Low was able to reverse these aging-like changes and restore nitric oxide production.
In older mice, Gly-Low treatment over four months significantly reduced arterial stiffness and lowered levels of MGO and MGH-1. This suggests the potential of Gly-Low to slow or even reverse vascular aging by mitigating glycation stress.
Exploring the Glyoxalase-1 Pathway
The researchers identified the glyoxalase-1 pathway as a critical mechanism in this process. 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 were nullified, underscoring the pathway’s importance.
“Aortic stiffness was assessed in vivo via pulse wave velocity (PWV) and ex vivo through elastic modulus,” the study notes, highlighting the comprehensive approach to measuring vascular health.
Implications for Future Therapies
The findings underscore glycation stress as a modifiable contributor to vascular aging, offering hope for new therapeutic strategies. Natural compound-based therapies like Gly-Low may provide a viable option to protect arteries from age- and diabetes-related damage.
According to corresponding authors Pankaj Kapahi and Zachary S. Clayton, this research opens new avenues for addressing cardiovascular risks associated with aging and metabolic disorders. The potential for Gly-Low to enhance the body’s natural detoxification pathways presents a promising strategy for future interventions.
Looking Ahead
While these findings are promising, further research is needed to confirm the efficacy of Gly-Low in human subjects. Clinical trials could pave the way for new treatments that target the underlying mechanisms of vascular aging, potentially improving the quality of life for millions of individuals worldwide.
The study’s DOI is available at https://doi.org/10.18632/aging.206335, providing access to the full research for those interested in exploring the detailed findings.
As the scientific community continues to explore the complexities of aging and metabolic health, the potential of natural compounds in therapeutic applications remains a promising frontier. The insights gained from this study could significantly impact the development of future cardiovascular treatments.
