Contesting the dogma of an age-related heat shock response impairment: implications for cardiac-specific age-related disorders

• Published in: Human molecular genetics 2014-07, Vol.23 (14), p.3641-3656
• Main Authors: Carnemolla, Alisia, Labbadia, John P, Lazell, Hayley, Neueder, Andreas, Moussaoui, Saliha, Bates, Gillian P
• Format: Article
• Language: English
• Subjects: Aging - physiology; Animals; Brain - growth & development; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; Gene Expression Regulation, Developmental - drug effects; Heart - growth & development; Heat Shock Transcription Factors; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Heat-Shock Response - drug effects; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Myocardium - pathology; Protein Folding; Pyridones - pharmacology; Pyrimidines - pharmacology; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddu073

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.