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Aging results in changes in the immune system, leading to both immune deficiency and inflammation. This cellular aging is closely linked to alterations in DNA methylation and histone modifications, which in turn result in disrupted gene expression patterns. We focus on understanding whether this phenomenon, often referred to as "epigenome aging," occurs in immune cells.

TRIM28, a nuclear protein that plays a critical role in gene repression through heterochromatin formation and in DNA repair. We have observed that TRIM28 becomes defective in aged immune cells. Specifically, the phosphorylation of TRIM28 decreases progressively with age in T cells and dendritic cells (DCs), indicating a dysregulation of gene expression in these cell populations related to the aging process. We generated mice lacking TRIM28 in immune cells. These mice have exhibited age-associated inflammatory and the de-repression of endogenous retroelements. For T cells, the deficiency of TRIM28 has been associated with impaired regulatory T cell function, adding to the immunosenescent phenotypes observed in these mice. We've also observed that uncontrolled inflammation resulting from TRIM28 deficiency can lead to systemic effects, which will be further discussed in our research.