Missing age-related AP-1 activation in ELLI
Presentation by Jörg Galle, Leipzig
Time: 12:00–12:30
Emergence of age-related B-cells (ABCs) is a phenomenon associated with immune aging. One can explain this process assuming a positive feedback loop, where ABCs secrete cytokines, which stimulate activator protein 1 (AP-1) pathway activity and activated AP-1 enforces ABCs specification. According to this model, aging is accompanied by permanent AP-1 activation.
We here analyze whether such activation occurs also in Exceptional Long-Living Individuals (ELLI), that typically show alleviated immune aging. For this purpose, we perform RNA-seq and EPIC arrays on matched sample of CD34+ cells obtained from peripheral blood of ELLI and aged Controls. We find significantly lower expression of AP-1 transcription factor subunits JUN, JUNB and FOS and of AP-1 targets in ELLI compared to Controls suggesting that ELLI are spared from age-related AP-1 activation. Increasing expression of JUN in these individuals is linked to hypo-methylation of DNA associated with repressive chromatin, a process frequently seen during lineage specification. Consistently, we observed disturbed cell population composition under permanent AP-1 activation in Controls, where the correlation is lost.
We discuss infections by pathogens as a potential AP-1 activating mechanism that seems to be suppressed by immune-modulatory genes such as HHLA2 in ELLI.