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Attenuated stress responses in young and old human lymphocytes
D A Jurivich1, L Qiu, J F Welk
1Department of Veterans Affairs, Northwestern University Medical School, Chicago, IL 60611, USA. jurivich@uic.edu
Mechanisms of Ageing and Development
|March 1, 1997
Summary
Aging impairs heat shock gene responses in human lymphocytes, potentially contributing to immunosenescence. Researchers identified non-responder cells with inhibited heat shock factor 1 (HSF1) DNA binding, suggesting a link between aging, replicative potential, and altered stress responses.
Area of Science:
- Molecular Biology
- Immunology
- Gerontology
Background:
- Aging is characterized by altered physiological stress responses.
- Heat shock genes are crucial for immune function and are affected by thermal stress.
- Senescent cells show perturbations in heat shock gene transcription, potentially linking thermal stress response to immunosenescence.
Purpose of the Study:
- To investigate the age-dependent changes in heat shock factor 1 (HSF1) DNA binding in human lymphocytes.
- To characterize non-responder lymphocytes that fail to induce HSF1-DNA binding after thermal stress.
- To explore the mechanisms underlying age-related diminished expression of heat shock genes.
Main Methods:
- Assessed HSF1-DNA binding in lymphocytes from young and old donors after heat shock (42°C).
- Characterized non-responder lymphocytes lacking HSF1-DNA binding post-heat shock.
- Investigated inhibitory activity in whole cell extracts from non-responder cells using HeLa cell HSF1.
- Examined the effect of heat denaturation and protease treatment on inhibitory activity.
- Used serial passage of lymphoblasts to model age-dependent changes in HSF1-DNA binding.
Main Results:
- Human lymphocytes exhibit an age-dependent loss in HSF1-DNA binding, with variability observed in both age groups.
- A subset of lymphocytes (non-responders) showed no HSF1-DNA binding after thermal stress.
- Whole cell extracts from non-responder cells inhibited HSF1-DNA binding in a heat-labile, non-protease-mediated manner.
- Serial passage of lymphoblasts recapitulated the loss of heat-inducible HSF1-DNA binding seen in aged lymphocytes.
Conclusions:
- Aging leads to an age-dependent loss of HSF1-DNA binding in human lymphocytes, contributing to altered thermal stress responses.
- The identification of non-responder cells and inhibitory factors suggests a novel mechanism for diminished heat shock gene expression with age.
- Loss of replicative potential and aging are linked to altered cellular stress responses, with potential implications for apoptosis and immunosenescence.