Depression caused by long-term stress regulates premature aging and is possibly associated with disruption of circadian rhythms in mice

Abstract

Depression has been associated with circadian disruption and premature aging. Nevertheless, mechanisms underlying the link between long-term stress with premature aging and possible associations with circadian rhythms remain elusive. Here, mice were exposed to chronic mild stress for 16 weeks to induce depression-like symptoms, which were confirmed with the open field test, tail suspension test, and sucrose preference test. Then, the circadian rhythms of age-related indexes were compared between control and stressed mice. Long-term stress resulted in decreased body weight gain and locomotor activities, accompanied by losses of subcutaneous backside fat, decreased amounts of thigh muscle fibers, and shortened telomere length in hepatocytes. Stressed mice showed increased oxidative damage, causing impaired mitochondrial function and inflammatory responses, which may be mediated by the sirtuin 3 (SIRT3)-superoxide dismutase 2 (SOD2) signaling pathway. These changes may be associated with partial disruption of circadian rhythms or shifting phase values of some age-related indicators induced by long-term stress. These findings suggest that long-term exposure to stress may increase the risk of depression and regulate age-related phenotypes through associations with circadian rhythms.