Epigenetic regulation of ImmuneAging: Heterochromatic DNA methylation as a regulator of T cell senescence (EpImAge)

Leibniz Competition Collaborative Excellence

The functional decline of the immune system with aging (ImmuneAging) is a major burden for elderly individuals leading to multiple age-associated diseases including chronic inflammation. T lymphocytes contribute to ImmuneAging by acquiring a senescent phenotype, which seems to result from  cumulative proliferation stress over the life-time of a human being.
We recently discovered a progressive, heterochromatin-restricted loss of DNA methylation, which correlated to the proliferation history of the cells.  We now hypothesize that this ‚proliferation-induced heterochromatic de-methylation‘ (PIHD) is functionally involved in the senescence process in T  cells.

In this collaborative project, we want:

• to define the molecular mechanism and the cellular consequences of PIHD,
• to compare the extent of PIHD in T cells during healthy conditions and during disease,
• to identify substances able to prevent or revert PIHD and hence, T cell senescence.

Cooperation partners: FLI Jena; FMP Berlin; IZW Berlin; Charité Universitätsmedizin Berlin; Universität des Saarlandes

Project term: 2018 – 2023