Gómez de Cedrón Marta, Moreno Palomares Rocío, Ramírez de Molina Ana
Molecular Oncology Group, IMDEA Food Institute, CEI UAM, CSIC, Madrid, Spain.
Cell Metabolism Unit, IMDEA Food Institute, CEI UAM, CSIC, Madrid, Spain.
Front Oncol. 2023 Jun 19;13:1169168. doi: 10.3389/fonc.2023.1169168. eCollection 2023.
Epigenetic modifications are chemical modifications that affect gene expression without altering DNA sequences. In particular, epigenetic chemical modifications can occur on histone proteins -mainly acetylation, methylation-, and on DNA and RNA molecules -mainly methylation-. Additional mechanisms, such as RNA-mediated regulation of gene expression and determinants of the genomic architecture can also affect gene expression. Importantly, depending on the cellular context and environment, epigenetic processes can drive developmental programs as well as functional plasticity. However, misbalanced epigenetic regulation can result in disease, particularly in the context of metabolic diseases, cancer, and ageing. Non-communicable chronic diseases (NCCD) and ageing share common features including altered metabolism, systemic meta-inflammation, dysfunctional immune system responses, and oxidative stress, among others. In this scenario, unbalanced diets, such as high sugar and high saturated fatty acids consumption, together with sedentary habits, are risk factors implicated in the development of NCCD and premature ageing. The nutritional and metabolic status of individuals interact with epigenetics at different levels. Thus, it is crucial to understand how we can modulate epigenetic marks through both lifestyle habits and targeted clinical interventions -including fasting mimicking diets, nutraceuticals, and bioactive compounds- which will contribute to restore the metabolic homeostasis in NCCD. Here, we first describe key metabolites from cellular metabolic pathways used as substrates to "write" the epigenetic marks; and cofactors that modulate the activity of the epigenetic enzymes; then, we briefly show how metabolic and epigenetic imbalances may result in disease; and, finally, we show several examples of nutritional interventions - diet based interventions, bioactive compounds, and nutraceuticals- and exercise to counteract epigenetic alterations.
表观遗传修饰是指在不改变DNA序列的情况下影响基因表达的化学修饰。具体而言，表观遗传化学修饰可发生在组蛋白上——主要是乙酰化、甲基化——以及DNA和RNA分子上——主要是甲基化。其他机制，如RNA介导的基因表达调控和基因组结构的决定因素，也会影响基因表达。重要的是，根据细胞环境和条件，表观遗传过程可驱动发育程序以及功能可塑性。然而，表观遗传调控失衡会导致疾病，尤其是在代谢性疾病、癌症和衰老的背景下。非传染性慢性病（NCCD）和衰老具有共同特征，包括代谢改变、全身代谢性炎症、免疫系统反应功能失调和氧化应激等。在这种情况下，高糖和高饱和脂肪酸摄入等不均衡饮食以及久坐不动的习惯，是与NCCD发展和早衰相关的风险因素。个体的营养和代谢状况在不同水平上与表观遗传学相互作用。因此，了解如何通过生活方式习惯和有针对性的临床干预——包括模拟禁食饮食、营养保健品和生物活性化合物——来调节表观遗传标记至关重要，这将有助于恢复NCCD中的代谢稳态。在此，我们首先描述细胞代谢途径中用作“书写”表观遗传标记的关键代谢物；以及调节表观遗传酶活性的辅助因子；然后，我们简要展示代谢和表观遗传失衡如何导致疾病；最后，我们展示一些营养干预——基于饮食的干预、生物活性化合物和营养保健品——以及运动来对抗表观遗传改变的例子。
