The Aging Brain

Aging is an important risk factor for the development of many chronic illnesses that increase functional disability and limit survival, including vascular disease, diabetes and dementia. These diseases are becoming increasingly prevalent in the US with the growth of our elderly population. One consistent finding in aging individuals and animals is the evidence of persistent low level elevations in circulating markers of inflammation, a phenomenon known as “inflammaging”. This pro‐inflammatory phenotype contributes to a global reduction in the capability of older individuals to cope with antigenic, toxic, physical and ischemic stressors. Elevated levels of inflammatory markers are strongly associated with increased risk for diabetes, coronary heart disease, frailty, stroke and mortality. Aging not only leads to higher baseline levels of systemic inflammatory markers, but also enhances baseline and stimulus‐induced pro‐inflammatory cytokine levels in the brain. Advanced age increased T cells, dendritic cells (DCs) and myeloid cells (primarily neutrophils) at the site of injury, which contribute to the exacerbated behavioral deficits in the aged. Our work has shown that dramatic age‐related changes are present in the microbiome, contributing to breakdown of the intestinal barrier, loss of bacterial containment, and chronic activation of the immune system with aging. In addition, accumulation of adipose tissue, up‐regulation of vascular adhesion molecules, and thymic involution lead to defects in cellular immunity in aged mice. Age‐related changes that occur in the brain will be reviewed. New research from our laboratory and from that of others suggesting that this age‐associated damage can be reversed will be discussed.