Human gene variant alters brain immune responses in aging mice
An experiment in male and female mice aged 6, 9 and 15 months found brain immune changes; behavioral impairments were most pronounced in older females.
Limit: Males retained their behavioral performance at all ages tested
Edited by Boris Djordjevic · AgingResearch.News
An experiment compared male and female mice engineered to carry HLA-DRB1*15:01, a human gene variant linked to multiple sclerosis, with unmodified controls at 6, 9 and 15 months. Researchers tested behavior and examined brain cells, tissue structure and immune signals.
Microglia, the brain’s resident immune cells, showed progressive immune changes and increased oxidative stress, stress from reactive molecules. The engineered mice also showed altered communication between brain support cells and greater accumulation of certain immune cells, particularly in females. Older engineered mice had disrupted organization of nerve fibers and their insulating covering in the hippocampus, a brain region involved in memory. Behavioral impairments were most pronounced in older females. Males retained their behavioral performance at all ages tested.
Why it matters
Age-related disruption of immune regulation is linked to chronic brain inflammation. The authors interpret their findings as insight into how a genetic risk factor for multiple sclerosis shapes vulnerability to that inflammation during aging.
Caveats
The engineered mice also lacked mouse versions of immune proteins that help cells recognize targets, complicating attribution to the human variant alone. These animal results do not establish what happens in people.
The paper
HLA-DRB1*15:01 drives sex- and age-dependent microglial immune phenotypes and neuroimmune signaling
University of Arizona
Frontiers in Immunology, Jun 16, 2026, Open access
