Do developmentally-related changes in constitutive proteolysis affect aberrant protein accumulation and generation of the aged phenotype?

This article considers whether developmentally-related changes in protein synthesis regulate constitutive cellular ability to degrade aberrant polypeptides and thereby contribute to the generation of the aged phenotype. It is suggested that low levels in constitutive ability to deal with aberrant proteins lower the threshold for induction of the stress response and increase cellular vulnerability to insults which characterizes the senescent state. It is proposed that developmentally-regulated diminution of constitutive proteolytic activities contribute to the onset of age-relate pathologies. (C) 2003 Published by Elsevier Science Ireland Ltd.