Chronic social stress in male mice induces a p16Ink4a-dependent accumulation of senescent cells in the hippocampus, cortex, peripheral blood mononuclear cells, and adipose tissue, accompanied by increased DNA damage and pro-inflammatory signaling.

When male mice experience long-term social stress, their cells produce excess harmful molecules that break DNA. This damage turns on a gene called p16Ink4a, which stops cells from dividing and forces them into a damaged, inactive state. These stuck cells release inflammatory chemicals that spread damage to nearby cells and tissues, including the brain, blood, and fat. Clearing these stuck cells removes the inflammation and reduces DNA damage.