Effects of aging on the motor, cognitive and affective behaviors, neuroimmune responses and hippocampal gene expression

•Impaired cognition and affective-like behaviors, and reduced locomotion have been reported during normal aging.•The effects of normal aging on brain functions in the absence of all external interventions are yet unclear.•Healthy C57BL/6 mice were housed and allowed to age in controlled environmental conditions devoid of all external interventions.•Aging reduced baseline locomotion, enhanced anxiety-like behavior, and impaired spatial memory. No effects on depressive-like behavior.•Aging affected microglia numbers in the dentate gyrus, peripheral CD8+ memory T cell count and the expression of hippocampal genes. The known effects of aging on the brain and behavior include impaired cognition, increases in anxiety and depressive-like behaviors, and reduced locomotor activity. Environmental exposures and interventions also influence brain functions during aging. We investigated the effects of normal aging under controlled environmental conditions and in the absence of external interventions on locomotor activity, cognition, anxiety and depressive-like behaviors, immune function and hippocampal gene expression in C57BL/6 mice. Healthy mice at 4, 9, and 14 months of age underwent behavioral testing using an established behavioral battery, followed by cellular and molecular analysis using flow cytometry, immunohistochemistry, and quantitative PCR. We found that 14-month-old mice showed significantly reduced baseline locomotion, increased anxiety, and impaired spatial memory compared to younger counterparts. However, no significant differences were observed for depressive-like behavior in the forced-swim test. Microglia numbers in the dentate gyrus, as well as CD8+ memory T cells increased towards late middle age. Aging processes exerted a significant effect on the expression of 43 genes of interest in the hippocampus. We conclude that aging is associated with specific changes in locomotor activity, cognition, anxiety-like behaviors, neuroimmune responses and hippocampal gene expression.