Scientists used single-cell RNA analysis to discover that supercentenarians — meaning people over 110 years of age — have an excess of an immune cell type called cytotoxic CD4 T-cells.
Scientists from the RIKEN Center for Integrative Medical Science (IMS) and the Keio University School of Medicine in Japan used single-cell RNA analysis to find that supercentenarians — meaning people over the age of 110 — have an excess of a type of immune cell called cytotoxic CD4 T-cells.
Supercentenarians are a little bit of an unique group of people. They’re extremely rare, first of all. For example, there were over 61,000 people over the age of 100 in Japan in 2015, but only 146 people over the age of 110.
Researchers have also found that these people have been relatively immune to diseases such as infections and cancer over their entire lives, leading to the possibility that they might have a particularly strong immune system, and the researchers have set out to find out what this may explain.
Then they also studied the circulating of immune cells from a group of supercentenarians and younger controls to answer the question. They obtained a total of 41,208 cells from seven supercentenarians (an average of 5,887 per subject) and 19,994 control cells (an average of 3,999 per subject) from five controls aged 50-80.
Researchers found that while in the supercentenarians the number of B-cells was lower, the number of T-cells was about the same, and in particular in the supercentenarians the number of one subset of T-cells was increased.
By analyzing these cells, the authors found that the supercentenarians had a very high level of cytotoxic cells, which means they could kill other cells, sometimes 80 percent of all T-cells, compared to just 10 or 20 percent of the controls.
T-cells with markers known as CD8 are usually cytotoxic, and those with CD4 markers are not, so the authors first thought they might have increased CD8-positive cells. But that turned out to not be the case. Rather, it seems the supercentenarians ‘ CD4-positive cells had gained cytotoxic status.
Intriguingly, when the researchers looked at the blood of young donors, there were very few CD4-positive cytotoxic cells, indicating that this was not a youth marker, but rather a special characteristic of the supercentenarians.
To study how these special cells were produced, the group examined in detail the blood cells of two supercentenarians and found that they arose from a process of clonal expansion, which meant that most of the cells were the progeny of a single ancestor cell.
According to Kosuke Hashimoto of IMS, the paper’s first author, “We were particularly interested in studying this group of people because we consider them a good model of healthy aging, and this is important in societies such as Japan, where aging is proceeding rapidly.”
Piero Carninci, Deputy Director of IMS, one of the group leaders, says, “This research shows how a study of single-cell transcription could help us understand how individuals are more or less susceptible to disease. CD4-positive cells generally work by producing cytokines, while CD8-positive cells are cytotoxic, and the combination of these two features that allows these individuals to be especially healthy. We think that this type of cell, which is relatively uncommon in most individuals, even young, are useful for fighting against established tumors, and could be important for immunosurveillance. This is exciting because it has given us new insights into how people who live long lives can defend themselves from conditions like infections and cancer.
The research released in the National Academy of Sciences (PNAS) Proceedings, was carried out in collaboration with scientists from the RIKEN Center for Integrative Medical Sciences and the School of Medicine at Keio University.


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