Biologie du Développement et Reproduction, UMR INRA-ENVA-CNRS 1198 BDR, Domaine de Vilvert, Bâtiment 231, F-78352 Jouy-en-Josas, France.
Proc Nutr Soc. 2010 May;69(2):221-31. doi: 10.1017/S002966511000008X. Epub 2010 Mar 5.
The phenotype of an individual is the result of complex interactions between genome, epigenome and current, past and ancestral environment leading to a lifelong remodelling of the epigenomes. The genetic information expression contained in the genome is controlled by labile chromatin-associated epigenetic marks. Epigenetic misprogramming during development is widely thought to have a persistent effect on the health of the offspring and may even be transmitted to the next generation. The epigenome serves as an interface between the environment and the genome. Dietary factors, including folate involved in C1 metabolism, and other social and lifestyle exposures have a profound effect on many aspects of health including ageing and do so, at least partly, through interactions with the genome, which result in altered gene expression with consequences for cell function and health throughout the life course. Depending on the nature and intensity of the environmental insult, the critical spatiotemporal windows and developmental or lifelong processes involved, epigenetic alterations can lead to permanent changes in tissue and organ structure and function or to phenotypic changes that can (or cannot) be reversed using appropriate epigenetic tools. Moreover, the flexibility of epigenetic marks may make it possible for environmental, nutritional and hormonal factors or endocrine disruptors to alter, during a particular spatiotemporal window in a sex-specific manner, the sex-specific methylation or demethylation of specific CpG and/or histone modifications underlying sex-specific expression of a substantial proportion of genes. Moreover, genetic factors, the environment and stochastic events change the epigenetic landscape during the lifetime of an individual. Epigenetic alterations leading to gene expression dysregulation accumulate during ageing and are important in tumorigenesis and age-related diseases. Several encouraging trials suggest that prevention and therapy of age- and lifestyle-related diseases by individualised tailoring to optimal epigenetic diets or drugs are conceivable. However, these interventions will require intense efforts to unravel the complexity of these epigenetic, genetic and environment interactions and to evaluate their potential reversibility with minimal side effects.
个体的表型是基因组、表观基因组和当前、过去和祖先环境之间复杂相互作用的结果，导致表观基因组的终身重塑。基因组中包含的遗传信息表达受不稳定的染色质相关表观遗传标记控制。发育过程中的表观遗传编程错误被广泛认为对后代的健康有持久影响，甚至可能传递给下一代。表观基因组作为环境和基因组之间的接口。饮食因素，包括参与 C1 代谢的叶酸，以及其他社会和生活方式暴露，对健康的许多方面都有深远的影响，包括衰老，并且至少部分通过与基因组的相互作用来实现，这导致基因表达改变，从而影响细胞功能和整个生命周期的健康。取决于环境损伤的性质和强度、涉及的关键时空窗口以及发育或终生过程，表观遗传改变可导致组织和器官结构和功能的永久性变化，或导致可（或不可）通过适当的表观遗传工具逆转的表型变化。此外，表观遗传标记的灵活性使得环境、营养和激素因素或内分泌干扰物能够在特定时空窗口以性别特异性的方式改变特定 CpG 和/或组蛋白修饰的性别特异性甲基化或去甲基化，从而改变性别特异性表达的大部分基因。此外，遗传因素、环境和随机事件会在个体的一生中改变表观遗传景观。导致基因表达失调的表观遗传改变在衰老过程中积累，在肿瘤发生和与年龄相关的疾病中很重要。几项令人鼓舞的试验表明，通过针对最佳表观遗传饮食或药物的个体化定制来预防和治疗与年龄和生活方式相关的疾病是可以想象的。然而，这些干预措施需要付出巨大努力来揭示这些表观遗传、遗传和环境相互作用的复杂性，并评估它们的潜在可逆性，同时尽量减少副作用。
