Open AccessMultifactorial Attenuation of the Murine Heat Shock Response With Age
Author(s) -
Donald Jurivich,
Gunjan D. Manocha,
Rachana Trivedi,
Mary Lizakowski,
Sharlene Rakoczy,
Holly M. Brown–Borg
Publication year - 2019
Publication title -
the journals of gerontology. series a, biological sciences and medical sciences
Language(s) - English
Resource type - Journals
eISSN - 1758-535X
pISSN - 1079-5006
DOI - 10.1093/gerona/glz204
Subject(s) - hsf1 , proteostasis , transactivation , biology , heat shock protein , heat shock factor , neurodegeneration , microbiology and biotechnology , medicine , hsp70 , genetics , transcription factor , disease , gene
Age-dependent perturbation of the cellular stress response affects proteostasis and other key functions relevant to cellular action and survival. Central to age-related changes in the stress response is loss of heat shock factor 1 (HSF1)-DNA binding and transactivation properties. This report elucidates how age alters different checkpoints of HSF1 activation related to posttranslational modification and protein interactions. When comparing liver extracts from middle aged (12 M) and old (24 M) mice, significant differences are found in HSF1 phosphorylation and acetylation. HSF1 protein levels and messenger RNA decline with age, but its protein levels are stress-inducible and exempt from age-dependent changes. This surprising adaptive change in the stress response has additional implications for aging and chronic physiological stress that might explain an age-dependent dichotomy of HSF1 protein levels that are low in neurodegeneration and elevated in cancer.