Age-related alterations of proteasome structure and function in aging epidermis

Recent studies on the effect of aging in epidermal cells have evidenced a d ecrease of proteasome activity and content, suggesting that proteasome is d own-regulated in aged cells. The 20S proteasome is the major proteolytic sy stem that has been implicated in removal of abnormal and oxidatively damage d proteins. Therefore, a decreased proteasome content may explain, at least in part, the well-documented age-related accumulation of oxidized proteins . To gain further insight in other mechanisms that may be implicated in a d ecreased activity of the proteasome with age, 20S proteasome has been purif ied from the epidermis from donors of different ages: young, middle-aged an d old. The patterns of proteasome subunits have been analyzed by 2D gel ele ctrophoresis to determine whether its structure is also affected with age. The 2D gel pattern of proteasome subunits was found to be modified for four subunits, indicating that the observed decline in proteasome activity with age may also be related to alterations of its subunits. These subunit alte rations are likely to be involved in the age-related decrease of proteasome activity since the specific peptidase activities of the purified proteasom e were found to be decreased with age. (C) 2000 Elsevier Science Inc. All r ights reserved.