People who live to exceptionally old ages may have immune systems that continue adapting to new health threats, according to a new study.
Researchers have found that supercentenarians — people aged 110 or older — have unusually high levels of specialised immune cells known as CD4 cytotoxic T lymphocytes (CD4 CTLs).
These rare immune cells can kill certain tumour cells and multiply quickly when the body faces an infection. The findings, published August 19 in the Cell Press journal Cell Reports, suggest that this immune response may be linked to healthy ageing in people who reach extreme old age.
“Immune ageing is not simply a process of decline,” said Kosuke Hashimoto, an associate professor at the University of Osaka in Japan and the study’s lead author.
Killer T cells increase with age
The researchers found that CD4 CTLs become more common as people reach very advanced ages. They examined blood samples from 28 people divided into three groups: those aged 70-99, 100-109 and 110 or older.
The average share of CD4 CTLs increased from 4% among those aged 70-99 to 9.6% among people aged 100-109. It rose further to 17.6% among those aged 110 and above.
The researchers said the increase may begin around the age of 100, although the pattern was not seen in every participant. One person under 100 had the highest level of CD4 CTLs recorded in the study.
Large immune cell groups
The team also examined T-cell receptors to understand why these cells become more common in some very old people.
Their findings suggested that clonal expansion — when immune cells make large numbers of copies of themselves after detecting a threat — plays an important role.
The largest single group of identical CD4 CTLs accounted for an average of 33.3% of all CD4 CTLs among the participants. In one centenarian, a single clone made up 53.8% of the person's CD4 CTLs.
The researchers compared the receptor sequences of these dominant cells with those in a public database. They found nearly three dozen matches among people diagnosed with lung, breast and liver cancers.
However, none of the centenarians or supercentenarians in the study had been diagnosed with those cancers.
The researchers suggested that the increased immune cells may be responding to abnormal cells or possible cancer-related targets, although their exact targets are still unknown.
Possible link to healthy ageing
The study does not prove that high levels of CD4 CTLs protect people from cancer or directly help them live longer. The researchers only examined immune cells circulating in the blood and said more work is needed to understand their role in body tissues.
Hashimoto said future research will focus on how these cells behave inside human tissues.
“As we age, abnormal cells, including ageing and cancerous cells, become more common,” he said. “Our findings suggest that the immune system’s ability to adapt to these changes may contribute to exceptional longevity.”
The study was supported by several Japanese research institutions and foundations, including the Japan Society for the Promotion of Science, the University of Osaka, the Takeda Science Foundation and the RIKEN Center for Integrative Medical Sciences.
Source: Science Daily