Secret of Supercentenarians: Excess of a Particular Immune Cell Type

Supercentenarians—people who live beyond 110 years—are very rare. General estimates say that this age is achieved by about one in 1,000 centenarians. For example, in Japan, there were more than 61,000 people over the age of 100 years in 2015, but among them just 146 were super centenarians. It has been found through studies that those who very rarely manage to live over 110 years are relatively immune to illnesses such as infections and cancer during their entire lifetime. This naturally raises some questions—is there any physiological specificity that these individuals with long lives are bestowed with and if there is any such thing, then what is that?

Scientists were curious about the presence of some speciality in the immune system of the super centenarians, which triggered researchers to study the immune system of these individuals.

The human immune system consists of special kinds of cells with distinct functions. Some of these cells find out whenever foreign objects get into the body while some fight with them and kill them, thus, conferring protection from infections. This fight between pathogens and the immune cells decides whether we escape infections or fall prey to them.

One type of the immune cell is called cytotoxic T cells. Now, researchers from the RIKEN Centre for Integrative Medical Science (IMS) and Keio University School of Medicine in Japan found that there is an excess of the cytotoxic T cells in the bodies of the super centenarians than others. Their research has been published in PNAS. The research team looked at circulating immune cells from a group of super centenarians and younger controls.

They acquired some 41,208 cells from super centenarians and 19,994 from controls. Their analysis showed that the number of one subset of T cells was in excess in the super centenarians. They reported that the super centenarians have a very high level of cells that are cytotoxic, meaning that they can kill other cells.

Again, T cells come with two varieties, distinct by markers present on them. They are the CD8 and CD4 markers. T cells having the CD8 marker are generally known to be cytotoxic whereas those with CD 4 markers are not. These made the researchers think that the super centenarians have CD8 positive cells in excess. To their surprise, the case appeared to be something else. They found that CD4 positive cells in the super centenarians acquired cytotoxicity. However, in the blood of young donors, they found that there were relatively few CD4 positive cytotoxic cells. The implication is that this is not a marker of youth but a special characteristic of the super centenarians.

The next step was to analyse how these special cells arose. The team went for detailed examinations of the blood cells of two super centenarians and found that they arose from the process of clonal expansion—cells coming from a single ancestor cell.

Kosuke Hashimoto, the lead author of the study says, “We were especially interested in studying this group of people, because we consider them to be a good model of healthy ageing, and this is important in societies like Japan where ageing is proceeding rapidly."

“This research shows how single-cell transcription analysis can help us to understand how individuals are more or less susceptible to diseases. CD4-positive cells generally work by generating cytokines, while CD8-positive cells are cytotoxic, and it may be that the combination of these two features allows these individuals to be especially healthy. We believe that this type of cells, which are relatively uncommon in most individuals, even young, are useful for fighting against established tumours, and could be important for immunosurveillance. This is exciting as it has given us new insights into how people who live very long lives are able to protect themselves from conditions such as infections and cancer,” IMS deputy director Piero Carninci said.