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Peer-reviewedCC BY-NC-ND 4.0NPJ Aging

Methylglyoxal engages aging-associated mechanisms to cause filtration impairment in nephrocytes

  • Lie Cheng1
  • Wan-Ju Yeh1,2
  • Fan-Chi Chang3
  • Hong-Wen Tang4
  • Chih-Chiang Chan1,5
  • Shuei-Liong Lin1,3
  • Shu-Yi Huang6
6 affiliations
  1. 1Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan
  2. 2Present Address: Graduate Program of Nutrition Science, School of Life Science, National Taiwan Normal University, Taipei, Taiwan
  3. 3Renal Division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  4. 4Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore
  5. 5Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan
  6. 6Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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Abstract

The decline of glomerular filtration is a hallmark of aging. Methylglyoxal (MG) is a uremic toxin known to induce aging-like changes; however, whether its mechanism of action is similar remains unclear. We compare the underlying mechanisms of MG and aging using Drosophila nephrocytes as a model. In addition to lower body weight, reduced locomotion, and shorter lifespans, MG caused filtration defects and induced cellular senescence in nephrocytes similar to the effects of aging, with a corresponding upregulation of the LXR/RXR signaling pathway. Mechanistically, we found that MG and aging both increased reactive oxygen species (ROS). Antioxidant treatments and inhibition of the LXR/RXR pathway both improved the filtration function. In addition, MG and aging both reduced the level of Jub, which is a protein essential for the integrity of the slit diaphragm structure. Overexpressing jub enhanced slit diaphragm structure and prevented MG-induced functional decline. Together, the findings reveal parallel features between MG and aging, and show that inhibiting LXR/RXR signaling, reducing ROS, or strengthening the slit diaphragm structure can preserve the filtration function of Drosophila nephrocytes.

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Cite

BibTeXRIS
BibTeX
@article{cheng2026methylglyoxal,
  title = {{Methylglyoxal engages aging-associated mechanisms to cause filtration impairment in nephrocytes}},
  author = {Lie Cheng and Wan-Ju Yeh and Fan-Chi Chang and Hong-Wen Tang and Chih-Chiang Chan and Shuei-Liong Lin and Shu-Yi Huang},
  journal = {NPJ Aging},
  year = {2026},
  month = jun,
  doi = {10.1038/s41514-026-00369-7},
  url = {https://doi.org/10.1038/s41514-026-00369-7},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Methylglyoxal engages aging-associated mechanisms to cause filtration impairment in nephrocytes
AU  - Lie Cheng
AU  - Wan-Ju Yeh
AU  - Fan-Chi Chang
AU  - Hong-Wen Tang
AU  - Chih-Chiang Chan
AU  - Shuei-Liong Lin
AU  - Shu-Yi Huang
PY  - 2026
DA  - 2026/06/04
JO  - NPJ Aging
DO  - 10.1038/s41514-026-00369-7
UR  - https://doi.org/10.1038/s41514-026-00369-7
AB  - The decline of glomerular filtration is a hallmark of aging. Methylglyoxal (MG) is a uremic toxin known to induce aging-like changes; however, whether its mechanism of action is similar remains unclear. We compare the underlying mechanisms of MG and aging using Drosophila nephrocytes as a model. In addition to lower body weight, reduced locomotion, and shorter lifespans, MG caused filtration defects and induced cellular senescence in nephrocytes similar to the effects of aging, with a corresponding upregulation of the LXR/RXR signaling pathway. Mechanistically, we found that MG and aging both increased reactive oxygen species (ROS). Antioxidant treatments and inhibition of the LXR/RXR pathway both improved the filtration function. In addition, MG and aging both reduced the level of Jub, which is a protein essential for the integrity of the slit diaphragm structure. Overexpressing jub enhanced slit diaphragm structure and prevented MG-induced functional decline. Together, the findings reveal parallel features between MG and aging, and show that inhibiting LXR/RXR signaling, reducing ROS, or strengthening the slit diaphragm structure can preserve the filtration function of Drosophila nephrocytes.
SN  - 2731-6068
ER  -