A recent new study explores the connection between psychological stress and stem cell aging. Research suggests that a complex axis involving the gut, brain and bone marrow may explain how emotional tension accelerates the cellular aging process. Understanding of the gut-brain axis had already expanded to include the gut microbiome, the immune system, and the endocrine system.
Mental health issues, such as psychological stress, can negatively influence the connection between the gut and the brain.
Now, new research has revealed a never-before-seen connection between the gut, brain and bone marrow.
Within this new interconnection, psychological stress is capable of modifying the intestinal microbiome, which can accelerate the aging of bone marrow stem cells, as observed in experiments with mice.
The existence of a connection between the brain and the intestine has been known for some time, forming the so-called gut-brain axis. This connection demonstrates that events in the brain can directly impact the gastrointestinal system, and vice versa.
More recent research has expanded this connection to include the gut microbiota, the immune system, and the endocrine system.
Mental health conditions such as depression, anxiety and psychological stress have been linked to negative impacts on the gut-brain axis in previous studies.
A new study, published in the scientific journal Cell Stem Cell, claims there is a link between the intestine, brain and bone marrow. In this interconnection, psychological stress can alter the intestinal microbiome, accelerating the aging of bone marrow stem cells, according to the mouse model.
Psychological stress: a risk factor for disease
For the study, researchers employed an animal model of psychological stress. The goal was to investigate the interaction between stress, the brain, intestines and bone marrow.
“Many people report increased susceptibility to colds or other illnesses during prolonged periods of psychological stress,” said Meng Zhao, PhD, professor at Sun Yat-sen University Zhongshan School of Medicine in China and senior author of the research.
“This common experience led us to question whether psychological stress suppresses immunity by affecting hematopoietic stem cells (HSCs), responsible for the production of all blood and the immune system,” explained Zhao.
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“Psychological stress is increasingly recognized as an important risk factor for many diseases, including cancer, cardiovascular and age-related disorders. However, we still know little about how emotional stress translates into biological signals that affect distant organs,” added Meng Zhao.
Stress compromises the production of stem cells in the bone marrow
At the end of the study, Zhao and his team concluded that stress impairs the self-renewal of hematopoietic stem cells (HSCs). Additionally, the production of lymphocytes, a type of white blood cell, was also reduced.
Investigating the mechanism behind this, researchers discovered surprising communication. The brain interacts with the bone marrow through sympathetic regulation of the intestinal environment and microbiota. This interaction alters microbiota-derived compounds, such as spermidine, a natural molecule linked to healthy aging, impacting the function of hematopoietic stem cells.
“When the brain experiences psychological stress, it sends signals through the sympathetic nervous system to the intestine,” explained Zhao. “These signals alter the gut environment and microbiota, decreasing the availability of beneficial metabolites such as spermidine. Without sufficient spermidine, HSCs lose the ability to maintain healthy blood and immune cell production.”
“In other words, emotional stress in the brain can indirectly influence the body’s immune system through the intestine,” Zhao said. He added: “As spermidine is a metabolite with broad biological functions, this mechanism may also affect organs other than the bone marrow.”
Next steps: confirm gut-brain-bone marrow axis in humans
Scientists observed that chronic stress decreased activity in two specific brain regions. The affected areas were the medial prefrontal cortex and the periaqueductal gray.
“To our knowledge, this is the first direct functional evidence that specific brain regions regulate the function of hematopoietic stem cells in the bone marrow,” Zhao said. “We found that suppression of these two stress-responsive brain regions was sufficient to reproduce many of the hematopoietic and immunological defects caused by psychological stress.”
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“These findings demonstrate that specific neural circuits actively regulate the function of immune stem cells, rather than just reacting to stress,” said the researcher. “More importantly, identification of these brain regions provides potential targets for developing new strategies to preserve immune function under chronic psychological stress.”
“Our next goal is to determine whether this brain-gut-bone marrow axis functions in a similar way in humans. Additionally, we want to know whether it contributes to immune dysfunction in aging, cancer and other chronic diseases,” Zhao added.
Connection of the brain and gut microbiome with other systems
Ashkan Farhadi, MD, gastroenterologist at MemorialCare Orange Coast Medical Center in Fountain Valley, California, commented on the study. He said the research adds another layer to understanding the role of stress throughout the body.
“We already had some notion about the brain-gut axis, with a strong bidirectional connection,” explained Farhadi, who was not involved in the study. “Recently, this axis has been expanded to include the brain-gut microbiome, and we have now extended it to other organs such as the bone marrow and overall body health.”
“Therefore, this study is very innovative, as it demonstrates that stress can begin to spread throughout the body through the intestine and its microbiome”, added the expert.
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Dung Trinh, MD, internist at MemorialCare Medical Group and medical director of Healthy Brain Clinic in Irvine, California, also agreed with the findings.
“This is a fascinating and important study because it connects several systems that we usually address separately: the brain, the gut microbiome, the immune system and aging,” said Trinh, who was not involved in the research.
“What caught my attention was that the researchers didn’t just say ‘stress is bad for the body'”, said Dung Trinh. “They mapped a plausible biological pathway in mice, showing how psychological stress can alter specific regions of the brain, modify the gut microbiota, reduce a protective metabolite called spermidine, and contribute to aging-like dysfunction in hematopoietic stem cells.”
“This makes the study especially convincing, although it is important to emphasize that this is still preclinical animal research, not proof that the same mechanism works in the same way in humans,” Trinh added.
Five tips for managing and reducing stress
For readers looking for ways to reduce stress, Rosario Ligresti, MD, chief of the Division of Gastroenterology at Hackensack University Medical Center in New Jersey, offered her top tips.
Ligresti highlighted breathing as one of the most powerful and simple tools for combating stress. He suggested a deep breathing exercise that can be performed anywhere and at any time to calm the nervous system:
- Find a comfortable position, sitting or standing.
- Inhale slowly and deeply through your nose for a count of four, allowing your belly to expand.
- Hold your breath for a brief moment.
- Exhale slowly through your mouth for a count of five, thinking of the word “relax.”
- Repeat this cycle 5 to 10 times, focusing on the sensation of your breath.
“Another effective way to reduce stress quickly is to move,” Ligresti said. “You don’t need an intense workout; even a simple 20-minute walk can do wonders to clear your mind and lessen feelings of stress.”
Physical activity, he explained, contributes to the release of endorphins and other neurotransmitters that improve mood.
“It also reduces the levels of stress hormones in your body,” he said. “Next time you feel overwhelmed, try going for a brisk walk. You might be surprised at how much calmer and more focused you feel afterwards.”
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Trinh also suggested other tips for reducing stress. These include prioritizing sleep and limiting factors that accelerate it, such as alcohol, caffeine and continuous exposure to news or social media, which can intensify stress responses.
“Loneliness and isolation can exacerbate stress,” Trinh continued. “Regular contact with friends, family, religious groups, support groups or community activities may be a protective factor.”
“Persistent anxiety, depression, symptoms of trauma, caregiver burden, or feelings of being overwhelmed are good reasons to talk to a primary care doctor or mental health professional,” the expert added.