Protein turnover plays a key role in aging
Section snippets
Increase in the concentration of damaged proteins during aging
Various genes have been identified in worms, flies and mammals whose mutation can drastically affect life span. For example, mutations in the insulin signaling pathway, such as age-1 and daf-2, can double life span in Caenorhabditis elegans (Friedman and Johnson, 1988, Kenyon et al., 1993), the Methuselah mutation can significantly increase life span in Drosophila (Lin et al., 1998), and mutation of p66shc can increase life span in mice (Migliaccio et al., 1999). However, the molecular
Protein turnover in aging
The rate of protein turnover is determined by the combined rates of protein synthesis and degradation. Once growth is complete, organisms reach a steady state in which the rate of protein synthesis equals the rate of protein degradation. Most studies of protein metabolism in aging were focused on protein synthesis, and there is overwhelming evidence that the rate of protein synthesis declines with age. This decrease in protein synthesis appears to be a universal phenomenon (reviewed in
Protein damage catastrophe
Although the age-dependent decrease in protein turnover is well-documented, the mechanism responsible for this decrease is unclear. Analysis of the literature suggests that the activities of various components of both the protein synthesis and degradation machinery decline with age (reviewed in Van Remmen et al., 1995, Cuervo and Dice, 2000, Grune, 2000, Friguet et al., 2000, Keller et al., 2000). A possible cause of such age-dependent decline in protein turnover can be the cumulative effect of
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