A recent study aimed to identify immune-specific patterns of ageing and exceptional longevity by analysing single-cell profiles from peripheral blood mononuclear cells (PBMCs) of 14 centenarians (mean age 106) and 52 individuals of younger age (20-89 years) using single-cell RNA sequencing (scRNA-seq). The analysis revealed known shifts in the ratio of lymphocytes to myeloid cells and noncytotoxic to cytotoxic cell distributions with ageing, as well as significant shifts from CD4+ T cell to B cell populations in centenarians, indicating a history of exposure to natural and environmental immunogens.
Furthermore, the examination of gene expression patterns revealed distinct characteristics in specific cell types associated with exceptional longevity.
These characteristics encompassed genes that exhibited changes related to age and genes that were exclusively expressed in the peripheral blood mononuclear cells (PBMCs) of centenarians.
These findings suggest that centenarians possess unique and highly functional immune systems that have adapted to a history of insults, allowing for exceptional longevity. The results provide insights into the immune mechanisms that underlie successful ageing and may help develop strategies to promote healthy ageing and prevent age-related diseases.
The role of senescent immune cells in ageing and longevity
Here are our key takeaways from the study, Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity.
Ageing leads to a decline in immune cell number and function
As we age, our immune system becomes less effective at fighting off infection. This is due to a number of factors, including a decline in the number and function of immune cells. For example, studies have shown that the number of T cells (a type of white blood cell) declines by about 20% per decade after the age of 20.
Additionally, the function of immune cells can decline with age. For example, T cells may become less responsive to antigens (substances that trigger an immune response). This can make it more difficult for the immune system to fight off infection.
Ageing leads to an increase in senescent immune cells
Senescent immune cells are cells that have stopped dividing and are no longer functional. They can accumulate in the body with age and contribute to the decline in immune function.
Senescent immune cells can release pro-inflammatory molecules that can damage surrounding tissues and cells. Senescent immune cells can also interfere with the function of healthy immune cells.
Senescent immune cells can contribute to infection, inflammation, and cancer
The decline in immune cell number and function, as well as the increase in senescent immune cells, can contribute to the increased risk of infection, inflammation, and cancer associated with ageing. For example, the decline in T cells can make it more difficult for the immune system to fight off infection.
Additionally, the release of pro-inflammatory molecules from senescent immune cells can contribute to inflammation. Inflammation can damage tissues and cells, and it can increase the risk of cancer.
Targeting senescent immune cells may be a promising approach for preventing age-related diseases
Targeting senescent immune cells may be a promising approach for preventing age-related diseases. Studies have shown that removing senescent immune cells can improve immune function and reduce inflammation. Additionally, removing senescent immune cells can slow the progression of age-related diseases, such as cancer and heart disease.
Reference: Karagiannis, Tanya T. et al. Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity. eBioMedicine, Volume 90, 104514. https://doi.org/10.1016/j.ebiom.2023.104514