image: Figure 4. Gly-Low treatment partially reverses transcriptomic alterations induced by GH overexpression. As shown in the experimental regime, bGH-Tg mice were treated with Gly-Low or control diet for 40 weeks, after which liver transcriptomes were analyzed. (A) Venn diagram shows 163 differentially expressed genes (DEGs) overlapping between Gly-Low–treated versus control bGH-Tg mice and bGH-Tg versus WT comparisons. (B) Correlation analysis of shared DEGs demonstrates a strong negative correlation (r = –0.50, p < 0.005), indicating that Gly-Low treatment counteracts transcriptional changes driven by GH excess. (C, D) Analysis of genes downregulated in bGH-Tg mice but restored by Gly-Low revealed enrichment of pathways associated with oxidoreductase activity, adenylate cyclase regulation, estrogen metabolism, and PPAR signaling, with TRRUST implicating transcription factors including SREBF1, ATF6, CLOCK, HNF1A, and NR1I2 as regulators. (E, F) Conversely, analysis of genes upregulated in bGH-Tg mice but suppressed by Gly-Low treatment identified enrichment of pathways related to actin filament–based movement, cAMP-mediated signaling, and gluconeogenesis, with TRRUST highlighting PPARA as a key transcriptional regulator.
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.
“Glycation-lowering strategies may serve as effective treatments for alleviating GH-induced metabolic and inflammatory disruptions in the liver, offering a promising avenue for addressing age-related metabolic diseases associated with GH dysregulation.”
BUFFALO, NY — November 18, 2025 — A new research paper was published in Volume 17, Issue 10 of Aging-US on October 3, 2025, titled “Growth hormone excess drives liver aging via increased glycation stress.”
In this study, led by first author Parminder Singh alongside with corresponding authors Pankaj Kapahi from the Buck Institute for Research on Aging and Andrzej Bartke from Southern Illinois University School of Medicine, researchers investigated how elevated growth hormone (GH) levels contribute to liver aging and dysfunction. They found that excess GH disrupts liver metabolism in ways that resemble aging-related liver damage. The study suggests that managing glycation stress may help prevent or treat liver diseases linked to abnormal hormone levels.
Excess GH is known to cause different disorders, but its long-term impact on internal organs like the liver has remained unclear. To address this, researchers used a mouse model engineered to overproduce bovine GH and examined how chronic hormone exposure affects liver function over time.
“Pathological conditions such as acromegaly or pituitary tumors result in elevated circulating GH levels, which have been implicated in a spectrum of metabolic disorders, potentially by regulating liver metabolism.”
The team found that young mice with GH overexpression showed molecular and cellular patterns similar to those in naturally aged livers. In both groups, genes involved in metabolism were suppressed, while those linked to immune and inflammatory responses were activated. On one hand, the metabolic changes were associated with the buildup of advanced glycation end products, harmful compounds formed when sugars attach to proteins or fats without proper regulation. On the other hand, the immune and inflammatory changes reflected a process known as “inflammaging,” a form of chronic, low-grade inflammation commonly associated with aging. By revealing the overlap between hormone-driven and age-related liver dysfunction, the study provides new insight into how GH may accelerate aging processes.
Importantly, the team showed that reducing glycation stress can reverse many of these negative effects. Mice treated with a compound that lowers glycation levels demonstrated improved liver health, reduced insulin resistance, and enhanced physical function. This intervention also corrected several abnormal genetic patterns caused by excess GH. The findings point to a potential therapeutic strategy for liver diseases associated with aging and hormonal imbalances.
Overall, this research identifies glycation and its byproducts as key contributors to liver damage caused by excess GH. It suggests that targeting glycation could offer broad therapeutic benefits, not only for hormone-related conditions but also for supporting liver health during aging.
DOI: https://doi.org/10.18632/aging.206327
Corresponding authors: Andrzej Bartke – abartke@siumed.edu; Pankaj Kapahi – pkapahi@buckinstitute.org
Abstract video: https://www.youtube.com/watch?v=6v8xi5muLwA
Keywords: aging, growth hormone, glycation stress, Gly-Low
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Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
Growth hormone excess drives liver aging via increased glycation stress
Article Publication Date
3-Oct-2025
COI Statement
The authors declare no conflicts of interest related to this study.