1. Academic Validation
  2. Dietary advanced glycation end-products exacerbate sarcopenia onset by activating apoptosis through PRMT1-mediated CRTC3 arginine methylation

Dietary advanced glycation end-products exacerbate sarcopenia onset by activating apoptosis through PRMT1-mediated CRTC3 arginine methylation

  • Cell Mol Life Sci. 2025 Apr 7;82(1):142. doi: 10.1007/s00018-025-05657-1.
Tian-Jin Huang 1 2 Shu Shang 1 2 Qin Wan 1 2 Qiang Li 1 2 Yang-Jingsi Li 1 2 Jin-Na Zheng 3 Fa-Xiu Chen 4 5
Affiliations

Affiliations

  • 1 Department of Geriatrics, Jiangxi Provincial People's Hospital, No. 92 Aiguo Rd, Donghu District, Nanchang, Jiangxi, 330006, China.
  • 2 Department of Geriatrics, The First Affiliated Hospital of Nanchang Medical College, No. 92 Aiguo Rd, Donghu District, Nanchang, Jiangxi, 330006, China.
  • 3 Medical College of Nanchang University, Nanchang, Jiangxi, 330006, China.
  • 4 Department of Geriatrics, Jiangxi Provincial People's Hospital, No. 92 Aiguo Rd, Donghu District, Nanchang, Jiangxi, 330006, China. fa-xiu.chen@hotmail.com.
  • 5 Department of Geriatrics, The First Affiliated Hospital of Nanchang Medical College, No. 92 Aiguo Rd, Donghu District, Nanchang, Jiangxi, 330006, China. fa-xiu.chen@hotmail.com.
Abstract

Background: Sarcopenia, the age-related decline in muscle mass and function, poses a major health risk to the elderly population. Although dietary advanced glycation end-products (AGEs) have been implicated in worsening sarcopenia, the precise molecular mechanisms remain unclear.

Methods: A sarcopenia animal model was established by feeding a high AGE diet to C57BL/6 mice. Muscle function and mass were assessed using grip strength tests, and rotarod tests. Proteomic analysis was used to identify differentially expressed proteins. Immunoprecipitation, mass spectrometry, and co-immunoprecipitation were employed to investigate protein interactions both in vivo and in vitro. Quantitative Reverse transcription PCR and Western blotting were conducted to measure gene and protein expression levels.

Results: Our results revealed that dietary AGEs accelerated the onset of sarcopenia in mice by triggering Apoptosis. Proteomic analysis showed a marked upregulation of protein arginine methyltransferase 1 (PRMT1) in the muscle tissues of mice fed a high AGE diet. PRMT1 mediated the arginine methylation of CREB-regulated transcription coactivator 3 (CRTC3) at the R534 site within its transactivation domain, leading to CRTC3 activation. The activated CRTC3, together with Forkhead box O3a (FOXO3a), transactivated the Bax (BCL2 associated X) gene, initiating Bax downstream signaling, promoting Apoptosis in muscle cells, and contributing to muscle atrophy. Inhibition of PRMT1 prevented CRTC3 methylation and suppressed Bax-mediated apoptotic signaling in vitro. Moreover, in vivo treatment with PRMT1 and Bax inhibitors significantly attenuated AGE-induced sarcopenia in mice.

Conclusion: PRMT1-mediated CRTC3 arginine methylation plays a critical role in AGE-induced sarcopenia and suggests potential therapeutic targets for preventing sarcopenia progression.

Keywords

Apoptosis; Arginine methylation; Bax; CRTC3; FOXO3a; PRMT1; Sarcopenia.

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