Appearance of biomarkers of in vitro ageing after successive stimulation of WI-38 fibroblasts with IL-1 alpha and TNF-alpha: senescence associated beta-galactosidase activity and morphotype transition

Sublethal oxidative stresses increase the proportions of human fibroblasts positive for senescence associated beta -galactosidase activity and acceler ate the transition in the fibroblast morphotypes characterising fibroblast ageing. Stimulation of fibroblasts with TNF-alpha or IL-1 alpha transiently increases the production of reactive oxygen species (ROS) in human fibrobl asts. Here we propose that repeated stimulation of WI-38 fibroblasts with T NF-alpha or IL-1 alpha can generate enough ROS to accelerate the transition in the fibroblast morphotypes and increase the proportion of cells positiv e for senescence associated beta -galactosidase activity. The involvement o f ROS is suggested by experiments where the stimulation of fibroblasts with TNF-alpha or IL-1 alpha are performed in the presence of N-acetylcysteine which increases the intracellular antioxidant potential. It is proposed tha t the decrease in the proportions of morphotypes I and II, and the increase in the proportions of morphotypes III to VI observed after successive stim ulation with TNF-alpha or IL1-alpha is attributed to an increased ROS produ ction occurring during the stimulation.