High levels of HDAC expression correlate with microglial aging

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. HDAC and microglial marker levels were examined in microglial cells after inducing senescence <i>in vitro</i> and in mouse and human hippocampal biopsies <i>in vivo</i>, using quantitative real-time PCR. Publicly available datasets were used to determine HDAC expression in different brain areas during physiological aging. 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 <i>HDAC1, 3</i>, and <i>7</i> and microglial and senescence markers. <i>HDAC1</i> and <i>3</i> levels are enriched in the purified aged microglial population. Several HDACs, particularly HDAC1, are elevated in microglia upon senescence induction <i>in vitro</i> and with aging <i>in</i> <i>vivo</i>, and correlate with microglial and senescence biomarkers.