Evidence mapPaperPMID 41247756Full record

ArticleAging2025

Methylglyoxal-induced glycation stress promotes aortic stiffening: putative mechanistic roles of oxidative stress and cellular senescence.

Parminder Singh, Ravinandan Venkatasubramanian, Sophia A Mahoney, Mary A Darrah, Katelyn R Ludwig, Alice Zhang, Kiyomi Kaneshiro, Lizbeth Enriquez Najera, Lauren Wimer, Muniesh M Shanmugam and 7 more

Abstract read
In one paragraph

Article in Aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Parminder SinghBuck Institute for Research on Aging, Novato, CA 94945, USA.
Ravinandan VenkatasubramanianUniversity of Colorado Boulder, Boulder, CO 80309, USA.
Sophia A MahoneyUniversity of Colorado Boulder, Boulder, CO 80309, USA.
Mary A DarrahUniversity of Colorado Boulder, Boulder, CO 80309, USA.
Katelyn R LudwigUniversity of Colorado Boulder, Boulder, CO 80309, USA.
Alice ZhangBuck Institute for Research on Aging, Novato, CA 94945, USA.
Kiyomi KaneshiroBuck Institute for Research on Aging, Novato, CA 94945, USA.
Lizbeth Enriquez NajeraBuck Institute for Research on Aging, Novato, CA 94945, USA.
Lauren WimerBuck Institute for Research on Aging, Novato, CA 94945, USA.
Muniesh M ShanmugamBuck Institute for Research on Aging, Novato, CA 94945, USA.
Edgard MorazanBuck Institute for Research on Aging, Novato, CA 94945, USA.
James J GalliganR. Ken Coit College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.
Marrisa N TrujilloR. Ken Coit College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.
Richmond SarpongCollege of Chemistry, University of Berkely, Berkely, CA 94720, USA.
Douglas R SealsUniversity of Colorado Boulder, Boulder, CO 80309, USA.
Pankaj KapahiBuck Institute for Research on Aging, Novato, CA 94945, USA.
Zachary S ClaytonUniversity of Colorado Boulder, Boulder, CO 80309, USA.

Funding

NHLBI NIH HHS K99 HL159241NIA NIH HHS R01 AG061165NIA NIH HHS R01 AG068288
6 · The paper itself

Abstract

backgroundHere, we assessed the role of the advanced glycation end-product (AGE) precursor methylglyoxal (MGO) and its non-crosslinking AGE MGO-derived hydroimidazolone (MGH)-1 in aortic stiffening and explored the potential of a glycation stress-lowering compound (Gly-Low) to mitigate these effects.

methodsYoung (3-6 month) C57BL/6J mice were supplemented with MGO (in water) and Gly-Low (in chow). Aortic stiffness was assessed

resultsMGO-induced glycation stress increased PWV in young mice by 21% (P<0.05 vs. control), which was prevented with Gly-Low (P=0.93 vs. control). Ex vivo, MGO increased aortic elastic modulus ~100% (P<0.05), superoxide production by ~40% (P<0.05), and MGH-1 expression by 50% (P<0.05), which were all mitigated by Gly-Low. Chronic MGO exposure elevated biomarkers of cellular senescence in HAECs, comparable to a known senescence inducer Doxorubicin, an effect partially blocked by Gly-Low. Moreover, elevated aortic elastic modulus induced by Doxorubicin (P<0.05 vs. control) was prevented with Gly-Low (P=0.71 vs. control). Aortic RNA sequencing implicated preservation of endogenous cellular detoxification pathways with Gly-Low following exposure to MGH-1. Old mice supplemented with Gly-Low had lower PWV (P<0.05) relative to old control mice.

conclusionsMGO-induced glycation stress contributes to aortic stiffening and glycation stress lowering compounds hold promise for mitigating these effects.

Indexed as

AortaCellular SenescenceGlycation End Products, AdvancedOxidative StressPyruvaldehydeVascular StiffnessAnimalsEndothelial CellsHumansImidazolesMaleMiceMice, Inbred C57BLPulse Wave AnalysisGlycation End Products, AdvancedImidazolesPyruvaldehydeglycation stressgly-lowmethylglyoxalpulse wave velocityvascular dysfunction

Identifiers

PMID41247756
PMCPMC12705182

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.