For decades, a mysterious, two-lobed organ nestled behind the breastbone has been overlooked by most physicians, thought to be a largely useless lump for most of human life: the thymus.
The ancient Greeks posited this knob of tissue might be the seat of the soul. In the early 1960s, a Nobel laureate dismissed it as a mere graveyard for cells, “an evolutionary accident of no very great significance.” Today, scientists know the thymus plays an essential role in setting up a functioning immune system in childhood, but then starts to rapidly shrink into obsolescence in puberty.
Now, a raft of research is recasting the thymus from a bit player to a potent regulator of aging and immune health across the lifespan.
Studies highlight the crucial role it might play in longevity, as well as protecting against cancer, autoimmune disease and cardiovascular risk. The work has ignited interest in finding ways to rejuvenate the thymus, slow its decay and better understand its function.
“It was completely assumed the thymus would become irrelevant,” said Hugo Aerts, director of the Artificial Intelligence in Medicine Program at Mass General Brigham. In studies published in Nature, Aerts and colleagues found that people with a healthier thymus were less likely to develop lung cancer or to die of heart disease — or any cause. They also responded better to cancer immunotherapy treatments.
Key questions remain: Is the thymus the driver of these improved health outcomes or an indirect barometer of better overall health? Why does its decline vary between different people, and can that be slowed or stopped? And, perhaps most fundamentally, why did it take so long to reconsider the thymus?
An accidental landmark study
The study that cast a new spotlight on the thymus started by serendipity.
Kameron Kooshesh, a medical student in David Scadden’s lab at Massachusetts General Hospital and the Harvard Stem Cell Institute, was interested in understanding the role of the thymus in a narrow population — adults who received bone marrow transplants. As those patients rebuild their immune defenses, researchers knew the thymus plays a role just as it does in childhood.
Then, covid shut everything down. The team shifted to an experiment that could be conducted remotely, broadening the research question: What did the medical records of adults who had their thymus surgically removed suggest about their overall health?
The findings stunned the team. In the five years after surgeons removed their thymus, people were more than twice as likely to die of any cause than a similar set of people who had undergone heart or chest surgery but still had one. Those without thymuses were twice as likely to develop cancer. When researchers limited the analysis to people who didn’t have immune-related issues before surgery, those lacking a thymus were more prone to autoimmune disease.
Full story: The body’s most mysterious organ may play a key role in longevity and cancer