Thymus gland research shifts focus to clinical trials for medical need, not longevity

Researchers are increasingly examining the thymus gland, an immune organ that naturally shrinks with age, for its potential role in extending longevity and improving cancer immunotherapy outcomes. Recent studies published in the journal Nature indicate that adults with a healthy-appearing thymus experience lower rates of cardiovascular disease and cancer, and show better responses to immunotherapy. While the organ does not disappear completely, it undergoes involution, replacing functional tissue with fat. Experts caution that current findings are correlational and that preserving thymic function may not guarantee extended lifespan, though it supports robust immune responses. Biotech firms are developing therapies to slow thymic shrinking, with clinical trials planned for next year, initially targeting patients with significant medical needs rather than healthy individuals seeking anti-ageing benefits.

The thymus is a gland located beneath the breastbone, in front of the heart, where T lymphocytes (T cells) mature. The organ is relatively large in newborns but gradually shrinks and becomes less active with age, a process known as involution, where functional tissue is replaced by fat and connective tissue. Paola Bonfanti, a professor at University College London’s Institute of Immunity and Transplantation, noted that the thymus begins to shrink during childhood and accelerates around puberty. Immune ageing is also caused by ageing of the bone marrow, changes in lymph nodes, and wear and tear on immune cells themselves. The thymus has been shown to regenerate itself in certain contexts, such as recovering after pregnancy, according to haematologist David Scadden.

In March, a team led by Harvard Medical School scientists published research in Nature, where they used AI to analyse thousands of CT scans. They found that adults with a healthy-appearing thymus lived longer and had lower rates of cardiovascular disease and cancer than those with an unhealthy thymus. In the same edition of Nature, a separate study analysing CT scans revealed that in patients with cancer, thymic health may influence response to immunotherapy, which is a treatment contingent on the strength of a patient’s immune system. Earlier, in 2023, a study revealed that people who had their thymus removed were three times more likely to die and twice as likely to develop cancer five years after its removal, compared with people who did not have their thymus removed.

Francisco Leon, chief executive of Tolerance Bio, stated the company is developing an antibody to slow thymic shrinking and will test it in clinical trials next year. The company has not revealed more details about the antibody, but they say they will test it in clinical trials next year. Bonfanti said that there is strong biological evidence that maintaining functional thymic tissue supports the production of new T cells and more robust immune responses. She added that studies are still needed to determine whether preserving or restoring thymic function can directly improve health or extend lifespan.

Bonfanti cautioned that current findings are correlational and do not establish cause and effect. It is equally plausible that healthier individuals are simply better able to preserve thymic tissue as they age, rather than a larger thymus being the reason they are healthier. If thymus regeneration proves to be safe and effective, the first recipients are unlikely to be healthy people seeking to slow ageing. Instead, the initial use will almost certainly be in patients with the greatest unmet medical need, where the potential benefits clearly outweigh the risks.