Immune system function declines with age. Immune cells become more inflammatory, but at the same time less capable. Further, populations of malfunctioning and harmful immune cells grow in number. The immune system is enormously complex, and one might argue that this is the primary reason why researchers have yet to produce a full accounting of the details of immune aging. Producing data is straightforward, but connecting the many different views of cell state that can be produced via omics technologies into a coherent whole is very much more challenging. Here, researchers focus on epigenetic changes, and the summary is illustrative of the present degree to which gene expression data can be readily connected to specific functions.
Epigenetic regulation, including DNA methylation and histone modifications, play a pivotal role in shaping T cell functionality throughout life. With aging, these epigenetic changes profoundly affect gene expression, altering T cell plasticity, activation, and differentiation. These modifications contribute significantly to immunosenescence, increasing susceptibility to infections, cancer, and autoimmune diseases.
In CD8+ T cells, chromatin closure at key regulatory regions suppresses activation and migration, while chromatin opening in pro-inflammatory gene loci amplifies inflammation. These changes drive terminal differentiation, characterized by increased expression of senescence-associated markers, impaired migration and loss of epigenetic plasticity. CD4+ T cells experience fewer but critical epigenetic alterations, including disrupted pathways, a skewed Th1/Th2 balance, and reduced Treg functionality. These epigenetic changes, compounded by metabolic dysfunctions, such as mitochondrial deficiency and oxidative stress, impair T-cell adaptability and resilience in the aging organism.
Understanding the interplay between epigenetic and metabolic factors in T cell aging offers promising therapeutic opportunities to mitigate immunosenescence and enhance immune function in aging populations.
Link: https://doi.org/10.1...929-025-01146-6
View the full article at FightAging
