The role of protein clearance mechanisms in organismal ageing and age-related diseases

We further describe how longevity-promoting pathways modulate the proteostasis network, providing increased stability of the proteome and protecting from the symptoms associated with neurodegenerative diseases

David Vilchez; Isabel Saez; Andrew Dillin

2014

Scholarcy highlights

  • The ability to maintain a functional proteome, or proteostasis, declines during the ageing process
  • Lysosomal proteolysis was initially considered to be a non-selective system, it has been shown that chaperones and other cargo-recognition molecules such as ubiquitins determine the degradation of specific proteins by the lysosome
  • We further describe how longevity-promoting pathways modulate the proteostasis network, providing increased stability of the proteome and protecting from the symptoms associated with neurodegenerative diseases
  • The decline in availability of chaperones during ageing, and in Hsp in the aged liver could explain the impairment in the trafficking and stability of lysosomal membrane-protein type 2A. These findings indicate that the loss of proteasome and autophagy may contribute to the ageing process
  • An intriguing question is whether adult somatic stem cells maintain their higher autophagy levels during organismal ageing and if a decrease in this activity could contribute to their senescence
  • Epidermal growth factor signalling promotes longevity in C. elegans. Upregulation of both proteasome activity and polyubiquitination, and a consequent decrease in protein aggregation are required for the lifespan extension induced by epidermal growth factor signalling
  • Further studies in mammals are required to strengthen the potential link between increased protein clearance mechanisms and the delayed onset of age-related disorders

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