Could cytotoxic T cells be a key to Longevity?

Scientists have used single-cell RNA analysis to find that supercentenarians – meaning people over the age of 110 – have an excess of an immune cell called cytotoxic CD4 T cells.

The human body contains more than 200 different cell types, each of which is responsible for carrying out a particular task. Hence, each of these cell types is equally important, and dysfunction in a specific cell type usually causes a disease related to the function that this type of cell is responsible for. However, a few cell types have been linked to a large number of diseases and conditions, and have therefore been at the forefront of biomedical research over the years.

T cells are undoubtedly one of these cell populations. Infectious diseases, autoimmunity, allergy, and cancer – you name it! No matter the disease, most probably there is going to be T cells involved to some extent. The fact that T cells are involved in a plethora of biological processes and health conditions is at least partly attributed to the flexibility and heterogeneity characterising them, as well as the existence of several subtypes with unique molecular profiles and functions. The number of T cell subtypes characterised is constantly increasing, and hybrids of these subtypes have also been identified [1].

Is there a direct role of cytotoxic CD4 T cells in extending life? Or is it solely through rendering us more resilient to lethal diseases, including cancer?


But are T cells or other immune cells linked to Longevity and healthy aging? And if so, how exactly do they achieve life extension and preventing age-related disorders?

Research conducted by Kosuke Hashimoto and colleagues from the RIKEN Center for Integrative Medical Science (IMS) and Keio University School of Medicine in Japan tried to address similar questions.

They focused on a rare part of the population, supercentenarians, who are people aged over 110 years. Interestingly, previous studies in supercentenarians have shown that they were less prone to immune-related diseases during their entire lifetime, suggesting a link between the immune system and longevity [2], [3].

They have performed single-cell transcriptome profiling of immune cells isolated from the blood of supercentenarians and compared it to younger individuals in their 50s to 80s. They found that even though the total number of T cells did not different profoundly between the two groups, supercentenarians had a much higher percentage of cytotoxic T cells, which is a T cell subset that can kill non-healthy cells. Intriguingly, even though cytotoxic T cells are traditionally known to express the CD8 marker but not the CD4, supercentenarians had much higher levels of the relatively newly characterized cell population of cytotoxic T cells that are CD4-positive, the percentage of which is very low in most individuals.

Even though these exciting findings suggest a role of cytotoxic CD4 T cells in healthy aging and Longevity, their role in humans remains unclear, and many open questions need to be addressed. Is there a direct role of cytotoxic CD4 T cells in extending life? Or is it solely through rendering us more resilient to lethal diseases, including cancer? Is the fact that this hybrid population combines the cytotoxic and helper functions provided by CD8 and CD4 T cells, respectively, what makes them so efficient in protecting from diseases? What are the mechanisms regulating the development of this cell population, and how can we implement them in novel interventions aiming to fight diseases and promote Longevity?

Even though T cell-based interventions have already entered the market through the commercialisation of chimeric antigen receptor (CAR) adoptive T-cell therapy for the treatment of certain malignancies, important questions need to be answered before we can use cytotoxic CD4 T cells to treat or prevent age-related diseases in humans.

We at Longevity.Technology are excited to explore this further and share with you the answers to these questions in the near future.