Some people live far beyond the average lifespan, reaching 100 or even 110 years. What sets them apart? A team at the University of Osaka in Japan has identified a striking difference in their immune systems: an unusually high number of a rare type of white blood cell.
The cells, known as CD4 cytotoxic T lymphocytes (CD4 CTLs), are part of the body's adaptive immune response. In younger adults, they typically make up less than 5% of T cells. But in supercentenarians—those aged 110 or older—their median proportion jumps to about 17.6%, according to a study published in the journal Cell Reports.
The researchers analyzed blood samples from 28 adults divided into three age groups: 70–99, 100–109, and 110 and older. The median percentage of CD4 CTLs rose with age: 4% in the youngest group, 9.6% in the centenarian group, and 17.6% in the supercentenarian group. This clear upward trend suggests that these cells expand and adapt as people reach extreme old age.
Why do these cells matter?
Aging is the result of molecular and cellular damage accumulating over time, leading to a gradual decline in physical and mental capacity and an increased risk of disease. However, the authors stress that aging itself is not a disease, nor does it inevitably cause the failure of essential bodily systems.
Supercentenarians are often considered models of healthy aging. They maintain immune, cardiovascular, and epigenomic profiles that appear younger than expected for their age, and they tend to avoid or delay major age-related diseases such as cardiovascular disorders and cancer. The new findings suggest that CD4 CTLs might play a role in this resilience.
“CD4 CTLs are an atypical and relatively rare T cell population,” said first author Kosuke Hashimoto, an associate professor at the University of Osaka. He added that their marked increase in supercentenarians may provide important clues as to how the immune system is maintained in extreme old age.
“The selective expansion of certain T cells suggests that, even in extreme old age, the immune system may continue to adapt to age-related challenges.”
The study proposes that these cells could contribute to longevity by targeting aging cells that accumulate in the body and by providing surveillance against tumors. This aligns with broader research into how the immune system changes with age, a topic of growing interest across Europe, where populations are aging rapidly.
For instance, pre-vaccination blood markers have been shown to predict how strongly people respond to vaccines, another sign that immune health is key to aging well. Similarly, nicotine in all forms harms the heart, a reminder that lifestyle choices affect longevity.
The authors caution that the research, which focused on T cells circulating in the blood, does not prove that an abundance of CD4 CTLs prevents cancer or directly causes longer life. Hashimoto said the team’s next step is to investigate how these cells behave in human tissue, where the real battle against aging and disease takes place.
While the study was conducted in Japan, its implications are global. European nations, from Germany to Italy, are home to some of the world’s oldest populations, and understanding the biology of extreme longevity could inform public health strategies. The findings also echo other recent discoveries about aging, such as eating disorders having distinct genetic roots, which highlight the complex interplay between genetics, environment, and health.
As research into supercentenarians continues, it may offer more than just curiosity. It could lead to new ways to delay age-related diseases and improve the quality of life for millions of Europeans and others worldwide.
