Proteasome function in aging and oxidative stress: implications in protein maintenance failure.

Damage to cellular components by reactive oxygen species is believed to be an important factor contributing to the aging process. Likewise, the progressive failure of maintenance and repair is believed to be a major cause of biological aging. Cellular aging is characterized by the accumulation of oxidatively modified proteins, a process that results, at least in part, from impaired protein turnover. Indeed, oxidized protein buildup with age may be due to increased protein damage, decreased elimination of oxidized protein (i.e., repair and degradation), or a combination of both mechanisms. Since the proteasome has been implicated in both general protein turnover and the removal of oxidized protein, the fate of the proteasome during aging has recently received considerable attention, and evidence has been provided for impaired proteasome function with age in different cellular systems. The present review will mainly address age-related changes in proteasome structure and function in relation to the impact of oxidative stress on the proteasome and the accumulation of oxidized protein. Knowledge of molecular mechanisms involved in the decline of proteasome function during aging and in oxidative stress is expected to provide new insight that will be useful in defining antiaging strategies aimed at preserving this critical function.