Clearance of p16Ink4a-positive senescent cells in chronically stressed male mice reduces senescence markers and DNA damage in the brain but does not improve stress-induced metabolic or physiological deficits such as hyperphagia, weight gain, or clinical frailty.

When an animal experiences long-term stress, its brain cells accumulate DNA damage from harmful molecules called reactive oxygen species. This damage turns on a gene called p16Ink4a, which stops the cells from dividing and forces them into a damaged, inactive state. These stuck cells release inflammatory chemicals that cause more inflammation and further damage in the brain. Removing these damaged cells reduces the inflammation and DNA damage in the brain, but it does not fix problems like overeating, weight gain, or physical weakness, because those issues come from other sources.