title: The role of protein clearance mechanisms in organismal ageing and age-related diseases.
abstract: The ability to maintain a functional proteome, or proteostasis, declines during the ageing process. Damaged and misfolded proteins accumulate with age, impairing cell function and tissue homeostasis. The accumulation of damaged proteins contributes to multiple age-related diseases such as Alzheimer's, Parkinson's or Huntington's disease. Damaged proteins are degraded by the ubiquitin-proteasome system or through autophagy-lysosome, key components of the proteostasis network. Modulation of either proteasome activity or autophagic-lysosomal potential extends lifespan and protects organisms from symptoms associated with proteostasis disorders, suggesting that protein clearance mechanisms are directly linked to ageing and age-associated diseases.
authors.affiliation: Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph Stelzmann Strasse 26, 50931 Cologne, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Vilchez
authors.affiliation: Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph Stelzmann Strasse 26, 50931 Cologne, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Saez
authors.affiliation: 1] Department of Molecular and Cell Biology, The University of California, Berkeley, Li Ka Shing Center for Biomedical and Health Sciences, Berkeley, California 94720, USA [2] Howard Hughes Medical Institute, The University of California, Berkeley, California 94720, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dillin
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D006706:Homeostasis; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D020543:Proteome; D013002:Somatomedins / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D007328:Insulin; D011506:Proteins; D020543:Proteome; D013002:Somatomedins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex