Laboratory of Ontogeny and Epigenetics, Pharmacology Department, Universidade Federal de São Paulo, São Paulo, Brazil.
Front Immunol. 2018 Feb 12;9:197. doi: 10.3389/fimmu.2018.00197. eCollection 2018.
Epigenetics refers to the study of mechanisms controlling the chromatin structure, which has fundamental role in the regulation of gene expression and genome stability. Epigenetic marks, such as DNA methylation and histone modifications, are established during embryonic development and epigenetic profiles are stably inherited during mitosis, ensuring cell differentiation and fate. Under the effect of intrinsic and extrinsic factors, such as metabolic profile, hormones, nutrition, drugs, smoke, and stress, epigenetic marks are actively modulated. In this sense, the lifestyle may affect significantly the epigenome, and as a result, the gene expression profile and cell function. Epigenetic alterations are a hallmark of aging and diseases, such as cancer. Among biological systems compromised with aging is the decline of immune response. Different regulators of immune response have their promoters and enhancers susceptible to the modulation by epigenetic marks, which is fundamental to the differentiation and function of immune cells. Consistent evidence has showed the regulation of innate immune cells, and T and B lymphocytes by epigenetic mechanisms. Therefore, age-dependent alterations in epigenetic marks may result in the decline of immune function and this might contribute to the increased incidence of diseases in old people. In order to maintain health, we need to better understand how to avoid epigenetic alterations related to immune aging. In this review, the contribution of epigenetic mechanisms to the loss of immune function during aging will be discussed, and the promise of new means of disease prevention and management will be pointed.
表观遗传学是指研究控制染色质结构的机制,它在基因表达和基因组稳定性的调控中起着基础性作用。表观遗传标记,如 DNA 甲基化和组蛋白修饰,是在胚胎发育过程中建立的,并且在有丝分裂过程中稳定地遗传,以确保细胞分化和命运。在内在和外在因素的影响下,如代谢谱、激素、营养、药物、烟雾和压力,表观遗传标记被积极地调节。从这个意义上说,生活方式可能会对表观基因组产生显著影响,从而影响基因表达谱和细胞功能。表观遗传改变是衰老和疾病(如癌症)的一个标志。随着衰老而受损的生物系统之一是免疫反应的下降。不同的免疫反应调节剂的启动子和增强子易受表观遗传标记的调节,这对免疫细胞的分化和功能至关重要。一致的证据表明,先天免疫细胞和 T、B 淋巴细胞受到表观遗传机制的调节。因此,与年龄相关的表观遗传标记的改变可能导致免疫功能下降,这可能导致老年人疾病发病率的增加。为了保持健康,我们需要更好地了解如何避免与免疫衰老相关的表观遗传改变。在这篇综述中,将讨论表观遗传机制对衰老过程中免疫功能丧失的贡献,并指出预防和管理疾病的新方法的前景。