A new preclinical study published in Cell Stem Cell has identified a potential biological mechanism through which chronic psychological stress accelerates immune aging. The findings suggest that prolonged stress disrupts communication between the brain, gut microbiota, and bone marrow, leading to aging-like changes in hematopoietic stem cells (HSCs)—the blood-forming stem cells responsible for generating immune cells.
Psychological stress is increasingly recognized as a major contributor to several chronic diseases, including cardiovascular disease, type 2 diabetes, and age-related disorders. Although previous studies have demonstrated that chronic stress impairs immune function through inflammatory pathways and activation of the body’s “fight-or-flight” response, the biological mechanism linking stress signals from the brain to dysfunction in the bone marrow has remained largely unknown.
To investigate this connection, researchers from Sun Yat-sen University employed four complementary mouse models of chronic psychological stress to examine interactions among the brain, gut, and bone marrow. The study revealed that chronic stress suppressed the activity of the medial prefrontal cortex and the periaqueductal gray, two brain regions that play key roles in regulating stress responses. This suppression was associated with depletion of hematopoietic stem cells and reduced production of lymphocytes, indicating impaired immune function.
The researchers also observed significant alterations in the gut microbiota of stressed mice. In particular, chronic stress markedly reduced the abundance of Lactobacillus reuteri, a beneficial bacterial species involved in maintaining intestinal microbial balance. This decline was accompanied by lower levels of spermidine, a microbial metabolite that supports cellular repair and the clearance of damaged cellular components.
According to the investigators, these stress-induced changes in the gut microbiota play a central role in transmitting stress signals from the brain to the bone marrow. “The finding of our study was that suppression of only two specific brain regions was sufficient to produce many of the hematopoietic defects caused by psychological stress,” the researchers stated. They further noted that alterations in gut microbes and reduced spermidine levels are key mediators of communication between the brain and the bone marrow.
Although the findings are based on animal models, the study provides important insights into the biological pathways through which chronic psychological stress may contribute to immune aging. The researchers suggest that targeting the gut microbiota or related metabolic pathways may represent a potential strategy for preserving bone marrow function during aging or prolonged stress, although this approach requires further investigation.
The authors emphasize that additional studies are needed to determine whether similar mechanisms operate in humans before these findings can be translated into clinical practice. Nevertheless, the study underscores the importance of effective psychological stress management, not only for maintaining mental well-being but also for preserving immune function and promoting healthy aging.
References
- Tian X, Wu B, Yang K, Wang Y, Li Y, Guan J, et al. Psychological stress drives aging-like hematopoietic stem cell dysfunction through a brain-gut-bone marrow axis. Cell Stem Cell. 2026.