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People who live beyond 110 appear to carry an unusually powerful population of immune cells that may help their bodies deal with cancerous and other abnormal cells. A new study found that supercentenarians have far higher levels of a rare type of immune cell called CD4 cytotoxic T lymphocytes, or CD4 CTLs.
Researchers at the University of Osaka analyzed blood samples from 28 people across three age groups and found that the proportion of CD4 CTLs increased substantially with age. The cells accounted for a median of 4% in people aged 70 to 99, 9.6% in those aged 100 to 109, and 17.6% in people aged 110 and older. The findings were published in Cell Reports.
CD4 CTLs are unusual because they combine characteristics typically associated with different types of T cells. They can help coordinate immune responses while also directly attacking target cells. Previous research has shown that these cells can kill tumor cells in some cancers.
The researchers found that the increase appears to begin around age 100. Their analysis also showed extensive clonal expansion, in which individual immune cells multiply after encountering a persistent target. The largest CD4 CTL clone accounted for an average of 33.3% of the cells in the participants studied. In one centenarian, a single clone represented 53.8%.
The team compared the receptors on these dominant immune-cell clones with sequences in a public database. Nearly three dozen matching sequences came from T cells found in patients with lung, breast, and liver cancers. None of the supercentenarians in the study had been diagnosed with those cancers.
The researchers say this could indicate that some of these immune cells recognize cancer-related targets, potentially helping the body identify abnormal cells before they develop into detectable disease. However, the study does not establish that CD4 CTLs prevent cancer or directly cause exceptional longevity.
“Immune aging is not simply a process of decline,” said Kosuke Hashimoto, the study’s first author. He said the selective expansion of certain T cells suggests the immune system can continue adapting to challenges even in extreme old age.
The researchers are now interested in studying these cells inside human tissues to better understand what they target and how they function. The findings suggest that healthy aging may involve not simply preserving the immune system, but actively reshaping it to respond to the threats that become more common with age.
