A Stolzing | PubMed Health

PubMed2001

Proteolysis, caloric restriction and aging.

The nature of the aging process has been the subject of considerable speculation. It is believed that free radical damage to cellular components is one of the main contributors to the aging process. Studies on proteins have shown age-related decline in enzyme activities, age-related accumulation of oxidized proteins and a decline of the proteolytic machinery of the cell. The proteasome, a highly regulated intracellular proteolytic system, is the major enzymatic system responsible for the degradation of damaged proteins. The current knowledge on regulation and of the properties of this unique proteolytic system with special emphasis to the aging process are discussed in this review. Since it is known that caloric restriction (CR) is the only method to delay the aging process and extend the maximal lifespan the effects of CR on the age-related decline in protein degradation is highlighted.

Aging↗

PubMed2001

The proteasome and its function in the ageing process.

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.

Aging↗