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Cytotoxic T Cells May Be A Key To Longevity

2 weeks, 2 days ago

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Posted on Nov 22, 2019, 3 p.m.

Single cell RNA analysis has revealed that supercentenarians, those are longevity warriors over the age of 110, have an excess of cytotoxic CD4 T cells in their immune systems which is typically very low in most people.

There are more than 200 different types of cells in the human body, and each is responsible for carrying out a particular task making each of these cells equally important, dysfunction in a specific cell usually causes a disease related to the function the cell is responsible for. A few cell types have been linked to a large number of conditions and diseases which have been at the forefront of biomedical research over the decades. 

T cells are one in this population, from infectious diseases and allergies to autoimmunity and cancer, no matter the disease chances are most probable that there is going to be T cells involved to some extent. T cells are involved in a plethora of biological processes and health conditions which can partly be attributed to their flexibility and heterogeneity that characterizes them, as well as there being several subtypes with unique molecular profiles and functions. Characterization and the number of T cell subtypes is constantly increasing, and hybrids of these subtypes are also being identified. 

Researchers from the RIKEN Center for Integrative Medical Science (IMS) and Keio University School of Medicine conducted a study to investigate whether T cells or other immune cells are linked to healthy aging and longevity, and how they might achieve their anti-aging and life extending abilities. 

Kosuke Hashimoto and colleagues focused on longevity warrior supercentenarians as previous studies have shown them to be less prone to immune related disease over the course of their entire lifetimes, suggesting this rare subset of the population may have a link between the immune system and longevity.

According to Kosuke Hashimoto of IMS, the first author of the paper, “We were especially interested in studying this group of people, because we consider them to be a good model of healthy aging, and this is important in societies like Japan where aging is proceeding rapidly.”

Single cell transcriptome profiling of immune cell was carried out on cells isolated from the blood of supercentenarians and compared to that from those in their 50s-80s. Results revealed that even though the total number of T cells did not vary greatly between the groups, the supercentenarians were found to have had a much higher percentage of cytotoxic T cells, which are a subset of T cells that kill non-healthy cells. Cytotoxic T cells are traditionally known to express the CD8 marker but not the CD4 markers, the longevity warriors had higher levels of the cell population of cytotoxic T cells that are CD4 positive which is very low in most people. 

Findings suggest a potential role of cytotoxic CD4 T cells in healthy aging and longevity, although that role and mechanisms regulating the development of this cell population remains unclear. It will likely still be some time before important questions are answered whether cytotoxic CD4 T cells can be used to treat or prevent age related disease in humans, but the encouraging findings are hoped to open new paths towards the implementation of novel interventions with the goal of fighting diseases and extending healthy aging and longevity.

IMS Deputy Director Piero Carninci, said, “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 tumors, 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.”

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