New research shows these hybrid immune cells ramp up after age 100 and stay active.
People who live past 110 carry an unusually large share of rare immune cells that can destroy infected or abnormal cells. A new analysis finds these cells expand sharply around the century mark and keep working without signs of burnout.
Researchers at the University of Osaka, working with colleagues including teams linked to Keio University, examined blood samples from 28 Japanese adults. The group included eight people aged 70–99, ten centenarians (100–109), and ten supercentenarians (110 and older). They profiled more than 40,000 T cells using single-cell methods.
What the numbers show
CD4 cytotoxic T lymphocytes, or CD4 CTLs, normally make up a small fraction of circulating T cells—typically under 5 percent. In the younger cohort the median share sat at 4 percent. It rose to 9.6 percent among centenarians and reached 17.6 percent in the supercentenarians. One healthy participant still under 100 carried the highest proportion of all.
These hybrid cells combine features of helper T cells and killer T cells. They can release signals that coordinate immunity while also directly attacking targets. The team found the cells showed no classic markers of exhaustion. Instead they displayed progressive differentiation, including loss of certain surface proteins that mark earlier stages.
Clones point to ongoing surveillance
Many of the CD4 CTLs belonged to large clones—identical copies of a single original cell. On average the most expanded clone made up about one-third of an individual’s CD4 CTL population. In one centenarian a single clone accounted for more than half. This pattern points to repeated encounters with the same persistent antigens over years.
Receptor sequences from the dominant clones matched some previously recorded in patients with solid tumors, especially lung cancer, even though the study participants had no recorded history of those cancers. The authors treat the overlap as a clue rather than proof of cancer surveillance.
“Immune aging is not simply a process of decline,” said lead author Kosuke Hashimoto. “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.”
Building on earlier work
The findings expand a 2019 single-cell study that first flagged elevated CD4 CTLs as a signature of supercentenarians. The new work shows the rise begins around age 100 and continues, driven by clonal expansion and functional plasticity. When stimulated outside the body, cells from the same clone produced varied cytokine profiles, hinting at flexibility.
The sample is small and limited to one country, so broader patterns remain to be confirmed. The team also notes that circulating cells may not fully represent tissue-resident populations, and direct protective effects in living people still need testing.
Still, the data challenge the view of late-life immunity as pure decline. In people who reach extreme ages, parts of the immune system appear to remodel in ways that may help counter rising threats such as cancer or reactivated viruses.
AI Disclosure: This article was created with the assistance of artificial intelligence tools and was reviewed and edited by the Glowls News editorial team before publication.