Cell senescence: hypertrophic arrest beyond the restriction point

Abstract

Withdrawal of mitogens (growth factors) arrests normal cells in G0 (quiescence). All other stresses and factors arrest cell cycle beyond the restriction point in G1 and G2 (non-G0 arrest), in the presence of mitogenic stimulation. Strong mitogenic stimuli by themselves cause non-G0 arrest. Unlike G0, arrest beyond restriction point is characterized by both high levels of cyclins and CDK inhibitors, activated mitogenic pathways with a secondary GF resistance, and continuous mass growth (cell hypertrophy). Prolonged hypertrophic arrest culminates in cell senescence. This review discusses that quiescence and senescence are two opposite, mutually exclusive conditions and that cell senescence can be reversed and prevented.