Super‑long‑lived individuals were found to have an abundance of immune cells

As the author of the study, Kosuke Hashimoto, an associate professor at Osaka University (Japan), explains, the aging of the immune system is not simply a gradual decline in its functions. The selective expansion of certain populations of T cells indicates that even at extremely advanced age, the immune system is capable of adapting to age‑related challenges. At the same time, CD4 CTL is an atypical and relatively rare population of T cells, so their pronounced increase in super‑centenarians may provide important clues about the mechanisms of maintaining immune defense in extreme old age.

During the study, experts analyzed blood samples from 28 adults divided into three age groups: 70–99 years, 100–109 years, and 110 years and older. It turned out that the proportion of CD4 CTLs consistently increases with age: the median values were 4%, 9.6%, and 17.6%, respectively. Although the increase in the proportion of these cells is particularly noticeable starting around the age of 100, this phenomenon is not an exclusive feature of long‑lived individuals: one of the participants under 100 years of age had the highest level of CD4 CTL among all those examined. The increase in the number of CD4 CTL is associated with the process of clonal expansion — the proliferation of cells that occurs when the immune system encounters a threat.

In the study, the most prominent clone accounted for an average of 33.3 % of the entire CD4 CTL population in the participants; in one case, in a 100‑year‑old person, the proportion of a single clone reached 53.8 %. This indicates that in older people, the immune system can actively respond to long‑standing threats. To understand what threats these clones are directed against, the scientists compared the receptor sequences of the dominant CD4 CTL clones of each participant with data from a publicly available database. Nearly three dozen matches were found in samples from people with oncological diseases — in particular, lung, breast, and liver cancer. At the same time, none of the examined long‑lived and super‑long‑lived individuals were diagnosed with these types of cancer. Researchers suggest that active proliferation of CD4 CTL may reflect early immune responses — the body likely recognizes and suppresses potentially dangerous cells even before a clinically evident tumor develops.

As Hashimoto notes, some CD4 CTLs are likely capable of recognizing targets associated with cancer, although the specific targets of their action remain unknown. It is important that the work is based on the study of T cells circulating in the blood and does not directly prove that a high concentration of CD4 CTLs prevents cancer or directly ensures an increase in life expectancy. The next step for the team is to investigate the behavior of these cells directly in human tissues. According to Hashimoto, as the body ages, it accumulates more abnormal cells — including aging (senescent) and potentially malignant ones. The data obtained suggest that the immune system’s ability to adapt to these changes may be one of the factors contributing to exceptional life expectancy.