title: Contesting the dogma of an age-related heat shock response impairment: implications for cardiac-specific age-related disorders.
abstract: Ageing is associated with the reduced performance of physiological processes and has been proposed as a major risk factor for disease. An age-related decline in stress response pathways has been widely documented in lower organisms. In particular, the heat shock response (HSR) becomes severely compromised with age in Caenorhabditis elegans. However, a comprehensive analysis of the consequences of ageing on the HSR in higher organisms has not been documented. We used both HS and inhibition of HSP90 to induce the HSR in wild-type mice at 3 and 22 months of age to investigate the extent to which different brain regions, and peripheral tissues can sustain HSF1 activity and HS protein (HSP) expression with age. Using chromatin immunoprecipitation, quantitative reverse transcription polymerase chain reaction, western blotting and enzyme linked immunosorbent assay (ELISA), we were unable to detect a difference in the level or kinetics of HSP expression between young and old mice in all brain regions. In contrast, we did observe an age-related reduction in chaperone levels and HSR-related proteins in the heart. This could result in a decrease in the protein folding capacity of old hearts with implications for age-related cardiac disorders.
authors.affiliation: Department Medical and Molecular Genetics, King's College London, 8th Floor Tower Wing, Guy's Hosptial, Great Maze Pond, London SE1 9RT, UK.
authors.forename: Alisia
authors.initials: A
authors.lastname: Carnemolla
authors.affiliation: Department Medical and Molecular Genetics, King's College London, 8th Floor Tower Wing, Guy's Hosptial, Great Maze Pond, London SE1 9RT, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Labbadia
authors.affiliation: Department Medical and Molecular Genetics, King's College London, 8th Floor Tower Wing, Guy's Hosptial, Great Maze Pond, London SE1 9RT, UK.
authors.forename: Hayley
authors.initials: H
authors.lastname: Lazell
authors.affiliation: Department Medical and Molecular Genetics, King's College London, 8th Floor Tower Wing, Guy's Hosptial, Great Maze Pond, London SE1 9RT, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Neueder
authors.affiliation: Novartis Institute for Biomedical Research, Neuroscience Discovery, Basel CH-4002, Switzerland.
authors.forename: Saliha
authors.initials: S
authors.lastname: Moussaoui
authors.affiliation: Department Medical and Molecular Genetics, King's College London, 8th Floor Tower Wing, Guy's Hosptial, Great Maze Pond, London SE1 9RT, UK gillian.bates@kcl.ac.uk.
authors.forename: Gillian P
authors.initials: GP
authors.lastname: Bates
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000254:growth & development*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000254:growth & development*; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009206:Myocardium / Q000473:pathology; D017510:Protein Folding; D011728:Pyridones / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C570862:2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido(4,3-d)pyrimidin-5(6H)-one; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C490017:Hsf1 protein, mouse; D011728:Pyridones; D011743:Pyrimidines; D014157:Transcription Factors