Protein Degradation in Health and Disease

Volume 29 of the series Progress in Molecular and Subcellular Biology pp 35-42

Protein Degradation in the Aging Organism

  • Walter F. WardAffiliated withDepartment of Physiology, University of Texas, Health Science Center at San Antonio

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Proteins are essential macromolecules that serve both as structural components of the cell and as its enzymatic machinery. The turnover of these proteins (synthesis + degradation) is a dynamic process that plays a critical role in the maintenance of cellular homeostasis. Because of their interest in the effects of the aging process on homeostasis, it is not surprising that geron-tologists have had a long-standing interest in the effects of age on protein turnover. Most of the reported studies have focused on the protein synthesis aspect of protein turnover, as opposed to protein degradation, and there is a general consensus that protein synthesis does indeed decline with age (Van Remmen et al. 1995; Rattan 1996; Ward and Richardson 2000). There are a number of likely reasons why more attention has been directed toward protein synthesis, beginning with the fact that cellular protein concentration appears to remain relatively constant with age, in the face of declining protein synthetic activity. This would then imply that protein degradation must also decline with age. Secondly, we have a better understanding of the mechanisms of protein synthesis than the mechanisms of protein degradation and, lastly, it is easier to measure protein synthesis than protein degradation.