Osaka, Japan – Aging while maintaining good health is a priority for many populations. This is often difficult considering that the risk of certain diseases increases with age, alongside weakened immunity to illnesses that younger individuals could easily overcome. This has raised an important question for researchers: why do some people live to a very old age while avoiding major diseases?
However, answers may come from new research, conducted by a team at the University of Osaka, involving Japanese supercentenarians aged 110 years and older. The findings suggest that a rare type of immune cell becomes increasingly abundant with extreme age. The findings are set to be published in Cell Reports.
One class of immune cells, called T cells, are traditionally divided into two groups: helper cells that coordinate immune responses, and killer cells that destroy infected or cancerous cells. However, supercentenarians accumulate an unusual hybrid known as CD4 cytotoxic T lymphocytes, or CD4 CTLs. These rare cells have the ability to both recognize threats and destroy dangerous cells.
To understand exactly how rare these hybrid cells are, immune cells from various age groups were analyzed. This included people in their 70s to 90s, centenarians, and supercentenarians. The hybrid cells remain uncommon throughout most of life but were found to expand dramatically around the age of 100. In supercentenarians, these cells make up nearly one-fifth of all T cells in the blood, whereas they only comprise about 4% of total cells in the younger study participants.
"We analyzed a rare cell population that is enriched in supercentenarians and found signs of immune remodeling in extreme old age," says lead author, Kosuke Hashimoto. "Rather than showing signs of exhaustion, they remain highly active and may help the body cope with persistent threats that increase with age."
Many of these cells had expanded into large populations of identical cells, suggesting that they had repeatedly encountered the same targets over the years. Remarkably, their molecular sensors closely matched those found on immune cells from patients with cancer, even though the supercentenarians had no history of the disease.
"The similarity between these receptor sequences and those found in T cells from tumors suggests that these cells may help recognize tumors before they become clinically detectable," says Hashimoto. "It may be that immune changes in extreme old age are better understood as the immune system reorganizing itself rather than just wearing out."
The researchers caution that their study does not prove that CD4 CTLs directly cause longevity. However, the findings provide one of the clearest pictures yet of how the immune system adapts in people who achieve exceptional lifespans, offering insight into healthy aging and potentially contributing to protection against disease in supercentenarians.
