People who live beyond age 110 may have unusually high levels of rare immune cells capable of destroying cancer cells.1 A study published in Cell Reports found that these cells, known as killer T cells, are especially common in supercentenarians. The findings suggest they may contribute to exceptional longevity by helping the body fight cancer and other threats. However, researchers emphasize that the study does not prove these cells extend lifespan, and their precise role remains unclear.
Supercentenarians—people aged 110 and older—not only live exceptionally long lives but also appear less likely to develop age-related conditions such as heart disease, dementia, and cancer. By studying the immune systems of these rare individuals, scientists hope to understand why they maintain good health for so long and identify potential ways to support healthy aging in the wider population.
“Most research on immunosenescence focuses on immune decline,” says study co-author Kosuke Hashimoto, a biologist at Osaka University. “Our study suggests that the immune system may continue to adapt selectively, even at extreme old age.”
Rare immune cells increase with age
The current study builds on findings published in 2019.2 Hashimoto and his colleagues found that supercentenarians have relatively high numbers of rare CD4 cytotoxic T lymphocytes, also called CD4 CTLs. These immune cells can destroy other cells and typically account for less than 5% of the body’s total T-cell population.
Although CD4 CTLs have received less attention than other T-cell types, growing evidence suggests that they become active during viral infections and may attack cancer cells, including lung cancer and melanoma cells. The researchers wanted to determine when these killer T cells begin to multiply in unusually high numbers.
Studying supercentenarians is challenging because so few people reach this age. In Japan, where the research was conducted, only about 150 people are estimated to be older than 110, according to Hashimoto. The study included 28 participants: eight people aged 70 to 90, 10 centenarians aged 100 to 109, and 10 supercentenarians.
Consistent with earlier research, the scientists found that CD4 CTLs were particularly abundant in supercentenarians. These cells were also present in high numbers among people aged 100 and older, suggesting that this immune adaptation may begin around the age of 100. In younger participants, CD4 CTLs made up approximately 4% of all T cells. The proportion increased to about 10% in centenarians and 18% in supercentenarians.
The researchers also found evidence that these killer T cells may respond to specific, long-lasting immune threats. Each T cell carries unique receptors that allow it to recognize particular antigens. When a T cell encounters its target, it can replicate, creating a group of genetically identical cells capable of attacking that threat.
In the study, a small number of identical cell clones made up most of the CD4 CTLs found in several centenarians and supercentenarians. In one centenarian, for example, 53.8% of the sampled cells were identical. This pattern suggests that the immune systems of these exceptionally long-lived individuals may have been repeatedly activated by persistent or specific triggers.
Because the CD4 CTLs were measured in blood samples, the researchers could not determine which tissues the cells entered or exactly what they did there. To investigate their possible function, the team analyzed receptors on the most common CD4 killer-cell clones and compared their amino acid sequences with a database of CD4 T-cell receptors.
About 30 sequences from the study matched receptor sequences found in cancer patients. The strongest matches were associated with lung cancer, even though none of the study participants had a history of cancer. The finding raises the possibility that these immune cells may recognize cancer-related targets, although further research is needed to confirm their role.
Adaptive immune response may support healthy aging
Source: www.nature.com