A novel role of Fas in delaying cellular senescence

Fas-mediated apoptosis is a major player of many physiological and pathological cellular processes. Fas-regulated immune regulation exhibits either the beneficial or the harmful effects which is associated with the onset or development of immune disorders. Alterations in apoptosis may contribute to age-associated changes. However, the role of apoptosis in the ageing process remains ambiguous. Here we demonstrated Fas signaling-mediated premature senescence in young mouse embryonic fibroblast (MEF) cells. Activated Fas signaling by agonist Jo-2 resulted in declined senescence in young and aged MEFs. Premature senescence induced the early activation of senescence markers, including the increase in the percentage of SA-beta-galactosidase (SA-beta-gal) cells, the induction of p53 phosphorylation, and the enhanced expression of p16 and p21 protein and elevated IL-6 pro-inflammatory cytokine in the absence of Fas. The elevated production of reactive oxygen species (ROS) in Fas-deficient MEFs was associated with dysfunctional mitochondria. Further, we determined that the known ROS scavenger NAC (N-acetyl-L-cysteine) could reverse the process of premature senescence in absence of Fas. Therefore, this study signifies a novel role of Fas in the control of cellular senescence.

Automated summary

Fas-mediated apoptosis plays a significant role in various cellular processes. The immune regulation controlled by Fas can have both beneficial and harmful effects on immune disorders. The role of apoptosis in the ageing process is still unclear, but this study shows that Fas signaling can induce premature senescence in mouse embryonic fibroblasts, while Fas deficiency leads to senescence through increased SA-beta-galactosidase activity, p53 phosphorylation, and the expression of p16, p21, and IL-6.