The secret to living past 110 may be an increase in killer cells in the bloodstream.
New research finds that "supercentenarians," or people who make it to 110 years of age or older, have higher-than-typical concentrations of a particularly rare type of T helper cell in their blood. These immune cells might protect the oldest of the old against viruses and tumors, leaving them in remarkably fine health throughout their long life spans.
"The key will be to understand what is [the cells'] their natural target, which may help to reveal what is needed for a healthy, long life," study co-authors Kosuke Hashimoto, Nobuyoshi Hirose and Piero Carninci wrote in a joint email to Live Science.
Secrets of supercentenarians
Carninci and Hashimoto are both researchers at the Riken Center for Integrative Medical Sciences in Japan, while Hirose is a scientist at the Centre for Supercentenarian Medical Research of the Keio University School of Medicine in Tokyo. They and their colleagues wanted to analyze the immune cells of supercentenarians because it had never been done before. People who live past 110 are rare even in Japan, where longevity is common and life expectancy reached over 81 years for men and over 87 years for women in 2018, according to government statistics. Japan’s 2015 census found that there were 61,763 people 100 years old or older living in the country that year, but only 146 who were 110 or older. (The world’s oldest person ever is usually cited as French citizen Jeanne Calment, who died at 122 in 1997, though those claims have been contested.)
Because supercentenarians are rare, it’s difficult to collect cellular samples from them. The new study focused on whole blood collection, because blood draws are relatively simple. The researchers isolated immune cells from the blood of seven supercentenarians and five control participants, ranging in age from their 50s to their 80s.
The scientists then used an advanced method called single-cell transcriptomics to find out what each of the immune cells was doing — individually. This method measures the messenger RNA produced by the hundreds of thousands of genes within a cell. Messenger RNA is the go-between that translates the genetic instructions of DNA to the nucleus of the cell, which uses those instructions to build proteins. By essentially reading the messages of the messenger RNA, researchers can determine the activities of each cell, effectively identifying it and its function.
The samples netted more than 41,000 immune cells from the seven supercentenarians and nearly 20,000 more from the younger control subjects. The standout finding, the authors said, was that a large proportion of the supercentenarians’ immune cells were from a subset called CD4 CTLs, a kind of T helper cell that can directly attack and kill other cells.
"This is surprising, because they are generally a rare cell type," Hashimoto, Hirose and Carninci wrote to Live Science.
The broad group of CD4 cells, or T helper cells, are generally not fighters. These cells are more like commanders, telling other immune cells what to do by releasing inflammatory chemicals called cytokines. But CD4 CTLs are cytotoxic, meaning they’re capable of actually attacking and destroying invaders themselves.
Usually just a few percent of all T helper cells are cytotoxic; the younger people in the new study showed an average of just 2.8%. But in the supercentenarians, about 25% of all helper Ts consisted of this deadly version, the researchers reported Tuesday (Nov. 12) in the journal Proceedings of the National Academy of Sciences.
The study can’t prove that the immune cells are the direct cause of extreme longevity. The researchers have since analyzed the blood of one centenarian, who also showed the same immune pattern, the study authors said. However, the sample size is still small. Cytotoxic T cells have been shown to attack tumor cells and protect against viruses in mice, the researchers said, but the next step is to figure out what these cells do in humans.
"One may expect to find some cancer antigens or some virus protein, but these are all speculations right now," the researchers said. "Yet, we hope to further explain why these humans could live in very good health for so long."