Aerobe living is consequently connected with a permanent oxidation of cellular proteins. Free radicals and other oxidants damage the normal intracellular protein pool. Therefore, the prevention of accumulation of oxidised cellular proteins is one of the major functions of the proteolytic machinery of mammalian cells. It is known that the multicatalytic proteinase complex, the proteasome, is the major protease that is able to recognise and degrade oxidised proteins.Cellular models are most useful to investigate biochemical changes of protein catabolism during senescence. Unfortunately, little is known about the protein turnover and the regulation of the proteasomal system as well as under oxidative stress conditions as during senescence. The proteasomal regulation during oxidative stress, protein oxidation and the changes of these processes during the ageing process are highlighted in this review.