Chronic, low-grade inflammation in the body (a phenomenon known as “inflammation” because it increases with age) is associated with many of today’s leading causes of disease and death, including cancer, heart disease, metabolic disease, and neurodegenerative diseases. But scientists have struggled to understand what causes inflammation or how to reverse its effects.
Researchers at the Keck School of Medicine at the University of Southern California have identified the thymus gland, a small organ behind the breastbone that plays a central role in the development of the immune system, as a key player in inflammation. They discovered that thymulin, a hormone produced by the organ, controls inflammation. As we age, thymulin decreases, inflammation increases, and diseases such as cancer can progress. In older mice, increased thymulin levels improved cancer survival and made immunotherapy more effective. The study was funded by the National Institutes of Health and was just published in the journal Science. nature communications.
This is the first evidence of a substance that is naturally produced in the thymus gland, decreases with age, and has the power to reverse age-related inflammation. ”
Fumihito Ito, MD, Professor of Surgery, Immunology, and Immunotherapy, Keck School of Medicine, lead author of this study
Recent research suggests that the thymus gland may be associated with chronic inflammation. The current discovery goes a step further and uncovers a biological mechanism that may actively drive the process. Thymulin may one day be tested in clinical trials as a way to treat cancer and other diseases.
“Taken together, these findings reveal pathways associated with aging, inflammation, and cancer immunity, and suggest thymulin as a potential strategy to improve cancer immunotherapy in older adults,” said Professor Ito, who is also deputy director of basic and translational science in the Department of Surgery.
Find the “factor of youth”
The research team’s discovery relied, in part, on an unusual research method known as heterochronic parabiosis. In this approach, researchers surgically join old and young mice together, allowing the two organisms to share blood flow. The procedure reduced inflammation in older mice, suggesting that something in young blood could help reverse age-related decline.
To identify that factor, researchers used both human blood samples and a mouse model. They analyzed genes associated with aging and longevity and focused on a list of candidates related to cytokines, signaling proteins that cause inflammation in the body. They noticed a noticeable pattern. Mice lacking either of these genes had thymus problems.
Dr. Ito and his colleagues began searching for biological pathways related to the thymus gland that could explain inflammation. Their tests revealed that thymulin, one of several hormones produced by the organ, regulates the body’s cytokines and helps control inflammation. As thymulin levels decline with age, cytokines increase.
“The thymus is best known for producing T cells that enable the immune system to fight infections and cancer, but our findings show that the thymus also helps suppress age-related inflammation,” Professor Ito said.
Chronic inflammation can also interfere with the immune system’s ability to attack tumors. Adding thymulin to older mice with cancer increased the immune response against tumors and improved overall survival. Addition of thymulin also made older mice more responsive to anti-PD-1/PD-L1 therapy, a type of cancer immunotherapy.
Thymulin and inflammation
This discovery raised new questions about the role of thymulin in cancer biology. Next, Ito and his colleagues plan to investigate whether this hormone affects tumor formation and spread.
In addition to cancer, many other conditions are thought to be linked to inflammation, including diabetes, chronic kidney disease, and Alzheimer’s disease. Professor Ito plans to work with experts at the Keck School of Medicine to investigate the role of thymulin in other chronic diseases.
This research could also have far-reaching implications for biomedical research. Insights from animal models often do not translate into successful clinical trials, and this study may help explain why. Although older mice are biologically different from younger mice, researchers often rely on younger animals because they are cheaper and easier to study.
“If we use young mice, we may be underestimating the effects of age-related chronic inflammation,” Ito says. “Studying older animals may be important for understanding age-related diseases.”
sauce:
Keck School of Medicine, University of Southern California
Reference magazines:
Kanemaru, H., Others. (2026). Thymulin suppresses age-related myeloid inflammation and enhances cancer immunotherapy. Nature Communications. DOI: 10.1038/s41467-026-75383-0. https://www.nature.com/articles/s41467-026-75383-0
