Supercentenarians have hypervigilant immune systems that fight off cancer

The immune systems of the oldest people on Earth may not slowly wind down, but instead go into overdrive, producing specialised cells that fight off ill health. A small study suggests that supercentenarians, who are older than 110, have high levels of a particular immune cell. This may be ramped up in response to the challenges faced in old age, such as a higher risk of cancer, which could be what’s driving their extreme longevity.

“I find it remarkable that even after more than a century of life, the immune system may still retain the ability to adapt,” says Kousuke Hashimoto at the University of Osaka, Japan. “Rather than simply declining with age, the immune system in these exceptionally old individuals may retain the ability to adapt to the persistent challenges that accumulate with age.”

In previous work, the researchers identified this immune cell – a type of T-cell called CD4 cytotoxic T lymphocytes (CD4 CTLs) – as being a distinctive marker of supercentenarians. For the new study, they wanted to quantify how these cells – which identify and kill threats such as cancer – change as we age.

They recruited eight people aged 70 to 99, 10 people aged 100 to 109, and an additional 10 people aged 110 and older. It may seem like a small number of individuals, says Hashimoto, but according to Japan’s national census, there are only around 150 supercentenarians in the country, “so 10 is a substantial number”.

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Blood samples revealed that as the groups aged, their percentage of CD4 CTLs as a proportion of their total T-cell count increased from 4 per cent to nearly 10 per cent, and then to more than 17 per cent among the oldest people.

The researchers also found that these immune cells didn’t show signs of T-cell exhaustion, a reduced ability to kill certain cells, such as cancerous ones or those infected by viruses. “Our findings suggest that [CD4 CTLs] may contribute to cancer immunosurveillance in extreme old age,” says Hashimoto.

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As we age, challenges to the immune system – such as abnormal cells like cancer and reactivated viruses – become more common. “We think CD4 CTLs may expand in response to these challenges and if we can understand why these cells expand in some very old people and what they attack, we may eventually be able to find ways to reproduce this beneficial immune response in others,” says Hashimoto.

Last September, Manel Esteller at the Sant Pau Research Institute in Barcelona, Spain, conducted a detailed study of María Branyas Morera, who was the world’s oldest woman before she died in 2024, aged 117 years and 168 days. Hashimoto’s research shows that supercentenarians are “enriched” in immune cells that attack threats to the immune system and probably also cancer cells, says Esteller.

“Maria underwent many infections but was able to defend against all of them,” he says. “She was the oldest [known] person in Spain that had the covid-19 virus and was asymptomatic.”

Source: Supercentenarians have hypervigilant immune systems that fight off cancer