Microglia in brain aging: An overview of recent basic science and clinical research developments

The process of aging is characterized by progressive tissue and organ degeneration, which is positively correlated with a higher mortality rate. The brain is one of the most affected organs. Age-related brain changes include abnormal neuronal activity, dysfunctional calcium homeostasis, dysregulated mitochondrial function and reactive oxygen species (ROS), all contributing to cognitive deterioration. Aging is therefore also one of the key risk factors in the development of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). For many years, neurodegenerative disease research has been concentrated primarily on neurons, with microglia cells receiving significantly less attention. Recently, microglial homeostasis has emerged as an important mediator in neurological disease pathogenesis. Here, we provide an overview of brain aging from the microglia's perspective. In doing so, we present the current knowledge on the relationship between brain aging and the microglia, summarize recent progress of research about the microglia in normal aging, AD, PD, Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), and then discuss the relationship between the senescent microglia and the brain. This will culminate with an understanding of the molecular complexity involved in the microglia in brain aging with suggestions for healthy aging.