The proteasome and its function in the ageing process.

Abstract

The ageing process is characterized by a progressive loss of function and a decline in the functional capacities of the organism, leading to death. The nature of the processes involved in loss of functions is not well understood. A number of theories have been proposed, including a hypothesis that emphasizes the role of reactive oxygen species as a fundamental causal factor in the ageing process; among other things, oxidative damage to proteins through reactive oxygen species plays a key role in the ageing process. Oxidative modification of proteins generally causes them to become dysfunctional, and normally to undergo preferential degradation. Within the cell the main proteolytic machinery involved in the degradation of oxidized proteins is the proteasomal system, consisting of a multicatalytic protease complex--the proteasome--and numerous regulatory factors. The proteasome is a highly conserved structure that is distributed in the cytosol, nucleus and endoplasmatic reticulum of mammalian cells. As the proteasome itself is also exposed to oxidative stress during the ageing process several studies were carried out to investigate the role and the activity of the proteasomal system during ageing. This review will describe current knowledge of the activity of the protesomal system and its possible involvement in the ageing process.