The thymus: The overlooked organ that may hold the key to longevity

Nestled beneath the sternum in the upper chest is a soft, overlooked organ that quietly shrinks with age.

This organ, the thymus, was named by the Greeks, who believed it was home to the soul. The word itself means soul in Greek.

Long seen as an organ that outlived its usefulness after childhood, the thymus is now attracting renewed interest. Scientists increasingly believe it could hold clues to one of humanity’s constant hopes — increasing longevity.

Here is more about the thymus, its function and the latest research about it.

What is the thymus?

The thymus is a gland located beneath the breastbone, in front of the heart. It is relatively large in newborns and is already well developed before birth, but it gradually shrinks and becomes less active with age.

The thymus is where T lymphocytes or T cells mature. Immature T cells first arise from stem cells in the bone marrow and then travel to the thymus. There, they develop into functional T cells, a type of white blood cell that can hunt down infected or cancerous cells and help coordinate the body’s immune response.

“The thymus begins to shrink surprisingly early in life, with the process starting during childhood and accelerating around puberty. It continues to decrease in size throughout adulthood,” Paola Bonfanti, a professor of epithelial cell biology and regenerative medicine at the University College of London’s Institute of Immunity and Transplantation, told Al Jazeera.

“As the thymus shrinks, its ability to produce new T cells, an essential part of the immune system, gradually declines. This loss of function can be measured by assessing the output of newly produced T cells in the blood.”

What have recent studies revealed?

Since the 1990s, researchers have been exploring whether halting its decline might strengthen the immune system and improve health in later life.

Now, new studies have added significant momentum to this approach, suggesting that the thymus may be critical for longevity and cancer immunotherapy response.

In March, a team led by Harvard Medical School scientists published research in the journal 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.

“However, these findings are correlational and do not establish cause and effect,” Bonfanti cautioned. “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.”

She added that studies are still needed to determine whether preserving or restoring thymic function can directly improve health or extend lifespan.

Nevertheless, 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.

“It is therefore reasonable to expect that preserving thymic function contributes to healthier immune ageing, although it should not be viewed as a guarantee of better overall health or longevity.”

Why was the thymus ignored for so long?

The thymus has been ignored because, for decades, doctors believed that the gland becomes completely inactive after puberty because it shrinks.

But in reality, “the thymus does not disappear completely, even in old age. Instead, it undergoes a process called involution, in which much of the functional thymic tissue is gradually replaced by fat and connective tissue,” Bonfanti explained.

“As a result, the organ becomes smaller and its capacity to produce new T cells declines. However, remnants of functional thymic tissue can still be found throughout life, although the amount varies considerably between individuals.”

However, Bonfanti explained that the thymus shrinking with age is only one reason our immune system ages. Immune ageing is also caused by ageing of the bone marrow, changes in lymph nodes and other lymphoid tissues or wear and tear on the immune cells themselves.

What does the new research mean?

Early studies suggest that a healthier thymus is linked to lower mortality and less disease, but researchers still don’t know whether regenerating the organ – and churning out more new T cells – will genuinely improve immune function or slow ageing in the long term.

“One of the best established indicators of thymic function is the number of newly produced T cells, measured using recent thymic emigrants in the blood, together with the diversity of the T cell repertoire,” Bonfanti said.

She explained: “As thymic activity declines with age, thus the production of new T cells and the diversity of the T cell population becomes more limited. These changes are associated with key features of immunosenescence, including reduced responses to vaccination, a diminished ability to respond to previously unseen infections, and a slower capacity to rebuild the immune system after treatments such as bone marrow transplantation.”

Scientists believe the thymus has the potential to regenerate itself. For instance, it atrophies during pregnancy but recovers after delivery, David Scadden, a haematologist at the Massachusetts General Hospital in Boston, said, as Nature reported.

What do we not know yet?

“We do not yet fully understand what drives the thymus to involute progressively with age, which exact cell populations are lost first, or which molecular signals prevent the tissue from shrinking,” Bonfanti said.

What’s next?

According to Nature, Francisco Leon, chief executive of the biotech company Tolerance Bio in Philadelphia, Pennsylvania, has said that his company is developing an antibody which slows down the shrinking of the thymus.

While the company has not revealed more details about the antibody, they say they will test it in clinical trials next year.

“If thymus regeneration proves to be safe and effective, the first recipients are unlikely to be healthy people seeking to slow ageing,” Bonfanti said.

“Instead, the initial use will almost certainly be in patients with the greatest unmet medical need, where the potential benefits clearly outweigh the risks.”