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<p>Erzhi Pills (EZP), a traditional Chinese herbal formula, has demonstrated potential aging-modulating properties, while its mechanisms in modulating immunosenescence remain incompletely understood. Two complementary aging murine models were employed to investigate the anti-immunosenescence efficacy of EZP, providing experimental validation for its translational application in delaying age-related immune decline. Morphological and physiological parameters were monitored and thymic/splenic organ coefficients were calculated. Histopathological evaluation of thymic involution was performed via hematoxylin–eosin (H&amp;E) staining. Flow cytometry quantified splenic T cell subsets (naïve/memory CD4<sup>+</sup> and CD8<sup>+</sup> T cells). Reverse transcription quantitative PCR (RT-qPCR) analyzed mRNA expression of key immunosenescence markers (Lin28a, GDF-11, Sirt1, IL-2, IL-17), while enzyme-linked immunosorbent assay (ELISA) measured serum levels of pro-inflammatory cytokines (TNF-α, IFN-γ). Metabolomic profiling further elucidated EZP's bioactive pathways. EZP administration significantly attenuated age-related degeneration in both murine models by restoring thymic and splenic architecture, as evidenced by increased organ coefficients and reduced histopathological damage. EZP rebalanced T cell homeostasis through selective expansion of naïve T cells and contraction of memory T cell subsets, with a pronounced increase in CD8<sup>+</sup> T cell populations. At the molecular level, EZP upregulated Lin28a, Sirt1, and IL-2 expression while modulating systemic cytokine profiles-reducing TNF-α and augmenting IFN-γ in the natural aging cohort. These findings suggest EZP mitigates chronic inflammatory aging and enhances immune responsiveness of effector T cells. EZP's anti-aging mechanism was mediated by&#xa0;fatty acid metabolism modulation. This study provides evidence supporting EZP's potential as a novel therapeutic strategy for immunosenescence and warrants further investigation into its clinical translation for geriatric populations.</p> Graphical abstract <p></p>

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Erzhi pills: a potential aging-modulating agent targeting immunosenescence in mice

  • 期刊论文

  • 发表日期：

    2026年3月2日

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  • Zhirui Fang,
  • Wei Sun,
  • Na Li,
  • Tingting Shi,
  • Xiuyun Ren,
  • Rui Zhang,
  • Yujing Zhang,
  • Jing Chen,
  • Qi Liu,
  • Meng Wang,
  • Lu Chen,
  • Hong Wang

摘要

Erzhi Pills (EZP), a traditional Chinese herbal formula, has demonstrated potential aging-modulating properties, while its mechanisms in modulating immunosenescence remain incompletely understood. Two complementary aging murine models were employed to investigate the anti-immunosenescence efficacy of EZP, providing experimental validation for its translational application in delaying age-related immune decline. Morphological and physiological parameters were monitored and thymic/splenic organ coefficients were calculated. Histopathological evaluation of thymic involution was performed via hematoxylin–eosin (H&E) staining. Flow cytometry quantified splenic T cell subsets (naïve/memory CD4+ and CD8+ T cells). Reverse transcription quantitative PCR (RT-qPCR) analyzed mRNA expression of key immunosenescence markers (Lin28a, GDF-11, Sirt1, IL-2, IL-17), while enzyme-linked immunosorbent assay (ELISA) measured serum levels of pro-inflammatory cytokines (TNF-α, IFN-γ). Metabolomic profiling further elucidated EZP's bioactive pathways. EZP administration significantly attenuated age-related degeneration in both murine models by restoring thymic and splenic architecture, as evidenced by increased organ coefficients and reduced histopathological damage. EZP rebalanced T cell homeostasis through selective expansion of naïve T cells and contraction of memory T cell subsets, with a pronounced increase in CD8+ T cell populations. At the molecular level, EZP upregulated Lin28a, Sirt1, and IL-2 expression while modulating systemic cytokine profiles-reducing TNF-α and augmenting IFN-γ in the natural aging cohort. These findings suggest EZP mitigates chronic inflammatory aging and enhances immune responsiveness of effector T cells. EZP's anti-aging mechanism was mediated by fatty acid metabolism modulation. This study provides evidence supporting EZP's potential as a novel therapeutic strategy for immunosenescence and warrants further investigation into its clinical translation for geriatric populations.

Graphical abstract