The article describes two main types of epigenetic changes, referred to as chromatin modifications or chromatin marks. They specifically analyze post-translational modifications (PTMs) of histone proteins and the incorporation of histone variants. Chromatin modifications encompass a wide range of chemical changes to histones, including phosphorylation, acetylation, and methylation. This refers to the exchange of standard histone proteins in the nucleosome with different versions, such as H3.3, H2A.Z, and macroH2A.

According to the article, aging has several effects on epigenetic modifications in immune cells. For one, the variation in chromatin marks, both between different individuals and within single cells of the same individual, increases with age. Another effect mentioned in the article is that the overall levels of most chromatin marks were found to be elevated in the immune cells of older subjects compared to younger subjects. An increased cell-to-cell variability in chromatin marks is referred to as “epigenomic noise.” The authors suggest this leads to higher “transcriptional noise,” meaning gene expression becomes less precise and more variable in aging cells. A study of twins revealed that these aging-related epigenetic alterations are predominantly driven by non-heritable, environmental influences accumulated over a lifetime.

In Figure 3, the paper analyzes the heterogeneity of chromatin in different lymphocyte subsets using the EpiTOF platform. The figure groups different T cell subsets based on their chromatin modification profiles to see which cell types are most similar epigenetically. It also directly compares the levels of specific chromatin marks between different functional subsets, such as naive vs. memory T cells and regulatory T cells vs. other T cells. The researchers used PCA to separate NK cell subsets based on the variation in their chromatin marks. The main result reported in Figure 3 is that different functional subsets of lymphocytes have distinct, specialized chromatin modification profiles.

The immune system comprises many distinct cell types, each with a unique epigenetic profile that defines its identity and function. Aging disrupts the usually stable and precise epigenetic regulation. As people age, the epigenetic profiles within their immune cells become more variable and less consistent, both within individuals and across different cells. These epigenetic changes are a molecular feature of aging in the immune system. The increased epigenomic noise that accumulates with age is linked to increased variability in gene expression. As aging occurs, the loss of precise epigenetic control could be an underlying mechanism for the decline in immune function that is a hallmark of the aging process.

References

Peggie Cheung, F. V. (2018). Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging. Cell, 173(6), 1385-1397. https://doi.org/10.1016/j.cell.2018.03.079.