A recent study published in the Journal for Infectious Disease found a potential explanation for the decline in immune response found in the elderly population. The culprit: telomeres.
To clarify, telomeres are the stretches of repetitive nucleotides with the sequence TTAGGG that exist at the end of chromosomes. Although they don’t code for any proteins, they have an extremely important function in the cell: to protect the genetic information that does code for proteins.
Each time a cell divides, it loses a few nucleotides from the ends of each chromosome during the replication process. In order to prevent cells from losing nucleotides that help code for proteins, we have protector sequences that act as a cushion for the chromosome. As time passes with cell division after cell division, these telomeres become shorter and shorter until there is nothing left, at which point the cell dies. This point is referred to as the Hayflick limit, or the number of cell divisions a cell can undergo.
The limiting effect of these “chromosomal cushions” is unique and has captured the attention of many scientists. Telomeres are currently seen as central actors in two fields, where they act in opposing roles. The gradual deterioration of telomeres has been implicated in the aging process; individuals eventually get to a point at which their cells can not longer replicate, leading to tissue damage.
As people get older, it is well known that they are no longer able to fight off infection as well as they once were able to. But why?
On the other end of the spectrum is the role of telomeres in cancer. Although normal cells are unable to do so, cells with more plasticity—such as stem cells or cancerous cells—are able to restore telomeres through the expression of the enzyme telomerase. In the case of cancer, the perpetual lengthening of telomeres is responsible for the continual growth of tumors.
This past year, Kevin Najarro and his team at the NIH investigated the role of telomeres in another process: immune response. As people get older, it is well-known that they are no longer able to fight off infection as well as they once were able to. But why?
Recent research has found some support for the role of telomeres in the diminishing capacity of the elderly to fight infections. The evidence, however, hasn’t been entirely convincing. For one, as the authors point out, the existing studies primarily use peripheral blood mononuclear cells (PBMCs), which is a large class comprised of a heterogeneous population of immune cells.
In hopes of trying to uncover the underlying details, Najarro’s research group honed in on key features of the immune system. The parts of the immune system known to decline in the elderly are the B cells, which make antibodies and proliferate when an antigen binds to their antibodies, and the T cells, which recognize and kill infected cells as well as regulate the overall immune response.
Telomeres were sequenced from adults older than 70 and categorized as long or short, depending on whether the length was within the upper or lower third of the sample. Participants were given the flu vaccine to study the immune response. After administration of the vaccine, the implicated immune features, including B cell antibodies and T cell proliferation, were analyzed and compared in adults with long and short telomeres.
Across the different measures of the immune response, the group saw consistent results. Individuals with longer telomeres produced higher levels of antibodies after receiving the flu vaccine. Additionally, their cytotoxic T cells—the ones that kill infected cells—proliferated more quickly than those with short telomeres. Collectively, these results provide evidence for the involvement of telomeres in the aging immune system.
Evidently, there is still much to learn about the role of telomeres in biology. As techniques for studying DNA and cells becomes easier and more available to research labs, we will undoubtedly see many more studies that investigate where else telomeres may be involved. Furthermore, many have suggested the potential use of telomerase in anti-aging drug therapies – if such drugs were to exist, perhaps they could also be useful in boosting immune response in immunosuppressed individuals.