Glia: victims or villains of the aging brain?

Aging is the strongest risk factor for metabolic, vascular and neurodegenerative diseases. Aging alone is associated with a gradual decline of cognitive and motor functions. Considering an increasing elderly population in the last century, understanding the cellular and molecular mechanisms contributing to brain aging is of vital importance. Recent genetic and transcriptomic findings strongly suggest that glia are the first cells changing with aging. Glial cells constitute around 50% of the total cells in the brain and play key roles regulating brain homeostasis in health and disease. Their essential functions include providing nutritional support to neurons, activation of immune responses, and regulation of synaptic transmission and plasticity. In this review we discuss how glia are altered in the aging brain and whether these alterations are protective or contribute to the age-related pathological cascade. We focus on the major morphological, transcriptional and functional changes affecting glia in a range of systems, including human, non-human primates, and rodents. We also highlight future directions for investigating the roles of glia in brain aging.