title: Aging and SKN-1-dependent Loss of 20S Proteasome Adaptation to Oxidative Stress in C. elegans.
abstract: Aging is marked by a collapse of protein homeostasis and deterioration of adaptive stress responses that often lead to disease. During aging, the induction of stress responses decline along with protein quality control. Here, we have shown that the ability to mount an adaptive response by pretreatment with minor oxidative stress is abrogated in aged Caenorhabditis elegans We have identified a defect in SKN-1 signaling sensitivity during aging and have also found an aging-related increase in basal proteasome expression and in vitro activity, however, adaptation of the 20S proteasome in response to stress is lost in old animals. Interestingly, increased activation of SKN-1 promotes stress resistance, but is unable to rescue declining adaptation during aging. Our data demonstrate that the aging-dependent decline in SKN-1 signaling negatively impacts adaptation of the 20S proteasome in response to acute oxidative stress.
authors.affiliation: Leonard Davis School of Gerontology.
authors.forename: Rachel
authors.initials: R
authors.lastname: Raynes
authors.affiliation: Leonard Davis School of Gerontology.
authors.forename: Crystal
authors.initials: C
authors.lastname: Juarez
authors.affiliation: Leonard Davis School of Gerontology.
authors.forename: Laura C D
authors.initials: LC
authors.lastname: Pomatto
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, and.
authors.forename: Derek
authors.initials: D
authors.lastname: Sieburth
authors.affiliation: Leonard Davis School of Gerontology, kelvin@usc.edu.|Division of Molecular and Computational Biology, Department of Biological Sciences of the Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles.
authors.forename: Kelvin J A
authors.initials: KJ
authors.lastname: Davies
mesh_terms: D000222:Adaptation, Physiological; D000375:Aging / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C073702:skn-1 protein, C elegans; D046988:Proteasome Endopeptidase Complex
keywords: Adaptive homeostasis; Hydrogen peroxide; Nrf2; Protein oxidation; Proteolysis