image: Figure 7. Gly-Low lowers MGO-induced glycation stress and aortic stiffening in old mice. (A) Treatment paradigm for Gly-Low supplementation in 20-month-old male mice. (B) Aortic stiffness as measured by PWV between two study groups (n=8/group). (C) MGO levels in plasma of mice that received control or Gly-Low enriched diet (n=9–10/group). (D) Plasma MGH-1 levels (n=9/group). (E, F) Ex-vivo study paradigm focusing on aortic stiffness in intervention-naïve male old (24–26 months) mouse aortas after 48-hour incubation in standard media (control) and Gly-Low (n=8). Panels (B), (C), and (D) were analyzed using unpaired t-tests, while panel (F) was analyzed using a paired t-test, as different media conditions were tested on aortas obtained from the same mouse. All values are in mean ± SEM, *p<0.05 vs. old control.
Credit: Copyright: © 2025 Singh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“MGO-induced glycation stress contributes to aortic stiffening and glycation stress lowering compounds hold promise for mitigating these effects.”
BUFFALO, NY — December 12, 2025 — A new research paper was published in Volume 17, Issue 11 of Aging-US on November 14, 2025, titled “Methylglyoxal-induced glycation stress promotes aortic stiffening: putative mechanistic roles of oxidative stress and cellular senescence.”
The study was led by first authors Parminder Singh of the Buck Institute for Research on Aging and Ravinandan Venkatasubramanian of the University of Colorado Boulder, with senior contributions from corresponding authors Pankaj Kapahi (Buck Institute for Research on Aging) and Zachary S. Clayton (University of Colorado Boulder and University of Colorado Anschutz Medical Campus). The researchers investigated how methylglyoxal (MGO), a toxic byproduct that builds up in blood vessels with age or metabolic dysfunction like diabetes, contributes to artery stiffening. Their findings are especially important to aging and diabetes-related cardiovascular risk.
Aortic stiffening, which reduces the flexibility of the body’s largest artery, is a key predictor of cardiovascular disease in older adults. The research team used young and aged mice to study how MGO affects vascular health. In young mice, chronic exposure to MGO increased aortic stiffness by 21%. However, when treated with Gly-Low, a supplement containing natural compounds such as nicotinamide and alpha-lipoic acid, this stiffening was completely prevented. Gly-Low also reduced the buildup of MGO and its harmful byproducts, particularly MGH-1, in both blood and tissue.
“Aortic stiffness was assessed in vivo via pulse wave velocity (PWV) and ex vivo through elastic modulus.”
The research showed that MGO’s damage goes beyond structural changes. It also caused the endothelial cells that line blood vessels to enter senescence, a state in which cells stop dividing and begin releasing inflammatory signals. This led to lower levels of nitric oxide, a molecule essential for blood vessel relaxation. In human vascular cells in lab culture, Gly-Low reversed these aging-like changes and restored nitric oxide production.
In older mice, which naturally develop stiffer arteries, Gly-Low treatment during four months significantly reduced stiffness and lowered MGO and MGH-1 levels. This suggests that Gly-Low may help slow or even reverse vascular aging by reducing glycation stress.
The study also identified the glyoxalase-1 pathway as a critical mechanism. This is a natural detox system that helps clear harmful molecules like MGO. Gly-Low appeared to boost this pathway. When the pathway was chemically blocked, Gly-Low’s protective effects disappeared, confirming its role in the process.
Overall, the findings highlight glycation stress as a modifiable contributor to vascular aging. The results suggest that natural compound-based therapies, like Gly-Low, may offer a potential strategy to protect arteries from age- and diabetes-related damage.
Paper DOI: https://doi.org/10.18632/aging.206335
Corresponding authors: Pankaj Kapahi – pkapahi@buckinstitute.org; Zachary S. Clayton – Zachary.Clayton@cuanschutz.edu
Abstract video: https://www.youtube.com/watch?v=i_rtq8eIb8c
Keywords: glycation stress, methylglyoxal, pulse wave velocity, gly-low, vascular dysfunction
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Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
Methylglyoxal-induced glycation stress promotes aortic stiffening: putative mechanistic roles of oxidative stress and cellular senescence
Article Publication Date
14-Nov-2025
COI Statement
Lauren Wimer, Neelanjan Bose, and Pankaj Kapahi are patent holders of GLYLO™, a supplement licensed to Juvify Bio by the Buck Institute. Dr. Pankaj Kapahi is the founder of Juvify Bio. The remaining authors have no conflicts of interest to declare.