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Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications
Published on: May 18, 2017
High levels of HDAC expression correlate with microglial aging
Jaione Auzmendi-Iriarte1, Leire Moreno-Cugnon1, Ander Saenz-Antoñanzas1
1Cellular Oncology Group, Biodonostia Health Research Institute, San Sebastian, Spain.
Background:
Cellular damage gradually accumulates with aging, promoting a time-dependent functional decline of the brain. Microglia play an essential regulatory role in maintaining cognitive activity by phagocytosing cell debris and apoptotic cells during neurogenesis. The activities of different histone deacetylases (HDACs) regulate microglial function during development and neurodegeneration. However, no studies have described the role of HDACs in microglia during physiological aging.
Research Design And Methods:
HDAC and microglial marker levels were examined in microglial cells after inducing senescence in vitro and in mouse and human hippocampal biopsies in vivo, using quantitative real-time PCR. Publicly available datasets were used to determine HDAC expression in different brain areas during physiological aging.
Results:
HDAC expression increased upon the induction of senescence with bleomycin or serial passage in microglial cultures. High levels of HDACs were detected in mice and aged human brain samples. Human hippocampal samples showed a positive correlation between the expression of HDAC1, 3, and 7 and microglial and senescence markers. HDAC1 and 3 levels are enriched in the purified aged microglial population.
Conclusions:
Several HDACs, particularly HDAC1, are elevated in microglia upon senescence induction in vitro and with aging in vivo, and correlate with microglial and senescence biomarkers.
Insights
Histone deacetylases (HDACs) increase in microglia as cells age and become senescent. This finding links HDACs to microglial function and brain aging.
Area of Science:
- Neuroscience
- Cell Biology
- Aging Research
Background:
- Cellular damage and brain aging lead to functional decline.
- Microglia are crucial for brain health, clearing debris and supporting neurogenesis.
- Histone deacetylases (HDACs) influence microglial function in development and neurodegeneration, but their role in aging is unknown.
Purpose of the Study:
- To investigate the role of HDACs in microglia during physiological aging.
- To determine if HDAC expression changes in senescent microglia.
Main Methods:
- Examined HDAC and microglial marker levels in vitro and in vivo using quantitative real-time PCR.
- Analyzed HDAC expression in aged mouse and human hippocampal samples.
- Utilized public datasets to assess HDAC expression in aging brain regions.
Main Results:
- HDAC expression increased in microglia induced to senesce in vitro.
- Elevated HDAC levels were found in aged mouse and human brain samples.
- HDAC1, 3, and 7 expression correlated with microglial and senescence markers in human hippocampi.
Conclusions:
- HDACs, especially HDAC1, are elevated in microglia during senescence and aging.
- Findings suggest a correlation between HDACs, microglial senescence, and aging biomarkers.
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