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<p>The review summarizes the context-dependent role of enhancer of zeste homolog 2 (EZH2) in cellular senescence and aging-associated tissue dysfunction. It discusses a conceptual shift from strong pharmacological EZH2 inhibition toward a more nuanced, context-dependent epigenetic modulation by natural compounds. Aging is associated with tissue‑specific alterations in EZH2 expression—both its decline and overexpression have been linked to cellular senescence, impaired regeneration, and age‑related pathologies, challenging the view of EZH2 as a purely oncogenic target. We critically assess the mechanisms by which natural compounds may influence aging and their potential relevance as candidate EZH2 modulators in geroprotection. The evidence suggests that careful EZH2 modulation may help restore epigenetic balance without disrupting essential chromatin functions. A deeper understanding of EZH2’s tissue-specific regulatory networks and downstream effectors is needed to develop safe, epigenetically balanced interventions targeting aging. This knowledge will be essential for advancing the development of novel, safe, epigenetically-targeted geroprotective therapies.</p>

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Natural modulators of enhancer of zeste homolog 2 (EZH2): potential epigenetic regulators of aging-associated pathways

  • 期刊论文

  • 发表日期：

    2026年7月3日

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  • Vassiliy Shmarin,
  • Zulfiia Guvatova,
  • Alexey Moskalev

摘要

The review summarizes the context-dependent role of enhancer of zeste homolog 2 (EZH2) in cellular senescence and aging-associated tissue dysfunction. It discusses a conceptual shift from strong pharmacological EZH2 inhibition toward a more nuanced, context-dependent epigenetic modulation by natural compounds. Aging is associated with tissue‑specific alterations in EZH2 expression—both its decline and overexpression have been linked to cellular senescence, impaired regeneration, and age‑related pathologies, challenging the view of EZH2 as a purely oncogenic target. We critically assess the mechanisms by which natural compounds may influence aging and their potential relevance as candidate EZH2 modulators in geroprotection. The evidence suggests that careful EZH2 modulation may help restore epigenetic balance without disrupting essential chromatin functions. A deeper understanding of EZH2’s tissue-specific regulatory networks and downstream effectors is needed to develop safe, epigenetically balanced interventions targeting aging. This knowledge will be essential for advancing the development of novel, safe, epigenetically-targeted geroprotective therapies.