Lymphocytes of super-long-livers
Employees of the RIKEN Center for Integrative Medical Science and the Keio University School of Medicine in Japan analyzed the RNA of single cells and found that super-long-livers, that is, people over 110 years old, have excessive activity of the immune system. The interest in studying these people is due to the fact that they can be considered a good model of healthy aging.
Super–long-livers are a pretty unique group of people. Firstly, there are very few of them. For example, in Japan in 2015 there were more than 61,000 people over 100 years old, but only 146 people over 110 years old. Secondly, studies have shown that these people are relatively immune to infections and oncological diseases throughout their lives. This led scientists to think that perhaps super-long-livers have a particularly strong immune system, and they decided to find an explanation for this fact.
The researchers studied circulating immune cells in the blood of super-long-livers and younger control group volunteers. They received a total of 41208 cells from seven super-long-livers (an average of 5887 per person) and 19994 cells for control (an average of 3999 per person) in five age groups from 50 to 80 years. They found that the number of B-lymphocytes was lower in super-long-livers, and the number of T-lymphocytes was about the same, and, in particular, the number of one of the types of T-cells was higher. Analyzing these cells, the authors found that super long-livers had very high levels of cytotoxic cells that are capable of killing other cells, they sometimes accounted for 80% of all T-lymphocytes, compared with 10-20% in the control groups.
Usually CD8 T-lymphocytes are cytotoxic, but CD4 T-cells are not, so the authors first thought that perhaps the super–long-livers had a higher number of CD8+ cells. But this is not the case. It turned out that CD4+ cells of super-long-livers acquired cytotoxic status. Interestingly, there were relatively few CD4+ cytotoxic cells in the blood of young donors, that is, they are not a marker of youth, but rather a special characteristic of super–long-livers. To see how these special cells appeared, the group studied in detail the blood samples of two super–long-livers and found that cytotoxic lymphocytes arose as a result of the process of clonal expansion - many of these cells were descendants of a single progenitor cell.
This study shows how the analysis of transcription of individual cells helps to understand how people are more or less susceptible to diseases. CD4+ cells usually work by producing cytokines, while CD8+ cells are cytotoxic, and perhaps the combination of these two traits allows super-long-livers to be especially healthy. The authors believe that this type of cell, which is relatively rare in most people, even young people, will be useful for fighting tumors, as well as for controlling the immune system.
Article by K. Hashimoto et al. Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians published in the journal Proceedings of the National Academy of Sciences (PNAS).
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on RIKEN materials: Could cytotoxic T-cells be a key to longevity?