Caretaker or undertaker? The role of the proteasome in aging

Maria Gaczynska, Pawel A. Osmulskil, Walter F. Ward

Research output: Contribution to journalReview articlepeer-review

75 Scopus citations


Despite intensive studies, the molecular basis of the decline of protein degradation with age still remains unresolved. It is suspected that the proteasome is one of the key factors controlling the age-dependent turnover of intracellular proteins. This hypothesis is based on the observation that the proteasome is a part of the ubiquitin-proteasome pathway, which together with the lysosomal pathway constitute the major mechanisms of protein degradation. While there are alterations in proteasome structure and function with age, the observed changes do not provide a clear mechanism for explaining the decline of protein degradation. In addition, there are no consistent changes in the ubiquitination system to account for this decline. On the other hand, because of the essential role played by the proteasome in the maintenance of cellular homeostasis, the observation of age-related changes in structure and function will ultimately be demonstrated to contribute to the aging process. The fact that food restriction, the only currently available experimental paradigm that can alter the aging process, modulates the age-related changes in proteasome structure and function provides presumptive evidence that the proteasome is involved in the aging process.

Original languageEnglish (US)
Pages (from-to)235-254
Number of pages20
JournalMechanisms of Ageing and Development
Issue number3
StatePublished - 2001


  • 20S proteasome
  • 26S proteasome
  • Aging
  • Caloric restriction
  • Ubiquitin

ASJC Scopus subject areas

  • Aging
  • Developmental Biology


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