Innovative anti-aging strategies targeting WNT pathway epigenetics for gut function

IF 0.5 Q4 GENETICS & HEREDITY

Human Gene Pub Date : 2025-03-05 DOI:10.1016/j.humgen.2025.201397

Yumna Khan , Ajay Singh Bisht , Sumel Ashique , Gyas Khan , Md Sadique Hussain

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Abstract

Objective

To explore innovative strategies targeting the Wnt/β-catenin signaling pathway and epigenetics to combat intestinal aging and preserve gut function.

Methods

This communication analyzes the role of Wnt signaling in intestinal stem cell (ISC) function, focusing on age-related changes and the interplay with epitranscriptomic modifiers such as YTHDF1 via m6A modifications. Additionally, the therapeutic potential of compounds derived from Traditional Chinese Medicine (TCM), including Eucommia ulmoides and Huankuile suspension, for Wnt pathway regulation is assessed.

Findings

Intestinal aging is associated with diminished ISC proliferation and compromised gut homeostasis due to involutional changes in Wnt signaling. YTHDF1 enhances FZD8 expression, reinforcing Wnt signaling and ISC preservation. TCM-derived compounds exhibit promising effects in restoring Wnt signaling activity and maintaining ISC multipotency.

Conclusions

Combining modern pharmacological insights with traditional medicine offers a novel, multifaceted approach to addressing intestinal aging by targeting Wnt pathway epigenetics, presenting a promising avenue for improving gut health.

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针对WNT通路表观遗传学对肠道功能的创新抗衰老策略

目的探讨Wnt/β-catenin信号通路和表观遗传学的创新策略，以对抗肠道衰老和维持肠道功能。方法本通讯分析Wnt信号在肠干细胞（ISC）功能中的作用，重点关注年龄相关的变化以及通过m6A修饰与YTHDF1等表转录组修饰因子的相互作用。此外，我们还评估了杜仲和环奎乐混悬液等中药衍生化合物对Wnt通路调控的治疗潜力。研究发现，肠道衰老与ISC增殖减少和肠道稳态受损有关，这是由于Wnt信号的变化引起的。YTHDF1增强FZD8表达，增强Wnt信号和ISC保存。中药衍生化合物在恢复Wnt信号活性和维持ISC多能性方面显示出良好的效果。结论将现代药理学与传统医学相结合，针对Wnt通路的表观遗传学为解决肠道衰老提供了一种新颖的、多方面的方法，为改善肠道健康提供了一条有前景的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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