High levels of HDAC expression correlate with microglial aging

Abstract

ABSTRACT 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.