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-β-galactosidase (SA-β-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.
Keywords: Apoptosis; Cellular senescence; Fas; Mouse embryonic fibroblast cells; Oxidative stress.
© 2023 The Authors.