Sick chaperones and ageing: a perspective

Ageing Res Rev. 2002 Apr;1(2):295-311. doi: 10.1016/s1568-1637(01)00005-8.


Intra- and extra-cellular protein deposits characterize many pathologic disorders (proteinopathies). These deposits contain different proteins, some of which are distinctive of a given disorder or type of disease, whereas others are not. The disorder-specific proteins are as a rule defective and have a tendency to misfold, aggregate, and precipitate-thus deposits are formed. The abnormal proteins typical of the better-characterized proteinopathies are not molecular chaperones, and the chaperoning systems in patients with these diseases are apparently normal. In this article, disorders in which abnormal chaperones seem to be the main pathogenetic factor are presented as a subset of the proteinopathies and termed chaperonepathies. A defective chaperone molecule (sick chaperone) will impact on the chaperoning system and pathway in which it normally participates. Since chaperones are ubiquitous their malfunctioning will have universal deleterious effects. In fact, the few known disorders in which a sick chaperone seems to be the main etiology, are clinically heterogeneous with many tissues affected. Senescence is characterized by a progressive decline of vigor and function throughout the body reflecting the failure of many molecules due to wear and tear, accumulation of mutations, and perhaps other factors. It is likely that this age-associated decline is due in part to a progressive failure of the chaperoning systems. Senescence would proceed even faster when a defective chaperone appears early in life due to a genetic defect. Furthermore, sick chaperones will make the individual vulnerable to stressors since the chaperoning systems are key anti-stress mechanisms. In this context, a combination of sick chaperones with stress appears as a driving force in the process of ageing.

Publication types

  • Review

MeSH terms

  • Aging / metabolism*
  • Aging / pathology*
  • Heat-Shock Proteins / chemistry
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / metabolism*
  • Protein Conformation


  • Heat-Shock Proteins
  • Molecular Chaperones