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.

Epigenetics of T cell aging

“…Any disarray in the epigenetic structure can result in cellular dysfunction. It is therefore reasonable to implicate epigenetic modifications in the pathologies associated with aging, if not even taking the bolder view to see the functionality of the epigenome as a major driver of the aging process, including immune aging . Here, we review how studies of the epigenetic landscape in human T cells are beginning to be informative to understand the mechanisms that drive T cell aging .…”

“…It is therefore reasonable to implicate epigenetic modifications in the pathologies associated with aging, if not even taking the bolder view to see the functionality of the epigenome as a major driver of the aging process, including immune aging. [9][10][11] Here, we review how studies of the epigenetic landscape in human T cells are beginning to be informative to understand the mechanisms that drive T cell aging. 12,13 In particular, we will discuss 2 not necessarily mutually exclusive explanations for age-associated epigenetic signatures; their resemblance to epigenetic pathways that drive aging in model organisms; and their relationship to epigenetic modifications that are seen with normal T cell differentiation.…”

Chemical Protein Degradation Approach and its Application to Epigenetic Targets

“…For example, other HDACs, methyltransferases, demethylases, and other modification enzymes are known,, and reader proteins, such as chromodomain proteins, have been discovered . However, sufficient discovery studies on inhibitors of chromodomain proteins are lacking ,. PROTACs targeting chromodomain proteins are of much interest as the next generation of epigenetic PROTACs.…”

Sleep Apnoea and Early Antecedents of Adult Disease

“…Numerous studies have subsequently documented associations between low birth weight and increased incidence of heart disease, hypertension, and type 2 diabetes, as well as relevant markers such as insulin resistance and dyslipidaemias 18,19 . Extrapolation of this early exposure linkage to other diseases such as cancer, neurodegenerative disorders and overall accelerated ageing has gained substantial traction in recent years, further attesting to the importance of internal and external environmental cues to the modulation of homeostatic processes, including those involved in tissue repair and regeneration [20][21][22][23][24][25] .…”