Abnormal Epigenetic Regulation of Immune System during Aging

Abstract

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.

Keywords: DNA methylation; age-related diseases; environment; epigenetics; histones; immune aging.

Figure 1

The epigenetic landscape, modulated by intrinsic and extrinsic factors, regulates immune system and contributes to define a healthy or pathological state. Our life style, including nutritional habit, exercises, life stressor, drugs, toxics exposition, and smoke, dynamically sculpts our epigenome along lifetime. The immune system is one of the systems in which functions are importantly regulated by epigenetic mechanisms. In this way, the accumulation of abnormal epigenetic marks in immune cells might contribute to the development of age-related diseases.