The immune system’s ability to fight against COVID-19 largely depends on its ability to replicate immune cells to destroy the SARS-CoV-2 virus effectively. These cloned immune cells can’t be mainly created.
A new study by the University of Washington suggests that the body’s ability to produce these cloned cells declines mainly in old age. The findings could answer why COVID-19 has such a devastating effect on the elderly.
With each division of DNA in cell division, the end cap — called a telomere — becomes shorter. A cell becomes too short after a series of replications, and at one point, it stops dividing. This limit does not apply to all cells or animals, but it applies to humans’ immune cells.
UW research professor James Anderson said, “The average person’s immune system coasts along pretty good despite this limit until about 50 years old. That’s when enough core immune cells, called T cells, have shortened telomeres and cannot quickly clone themselves through cellular division in big enough numbers to attack and clear the COVID-19 virus, which has the trait of sharply reducing immune cell numbers.”
“Importantly, telomere lengths are inherited from your parents. Consequently, there are some differences in these lengths between people at every age and how old a person becomes before these lengths are mostly used up.”
“The key difference between this understanding of aging, which has a threshold for when your immune system has run out of collective telomere length, and the idea that we all age consistently over time is the “most exciting” discovery of his research.”
“Depending on your parents and very little on how you live, your longevity or, as our paper claims, your response to COVID-19 is a function of who you were when you were born. It is a kind of big deal.”
For this study, scientists developed a model of telomere length (TL)-dependent T-cell clonal expansion capacity with age. Using the model, they virtually examined the relation of T-cell clonal expansion with COVID-19 mortality in the general population.
Their model shows that an individual with average hematopoietic cell TL (HCTL) at the age of twenty years maintains maximal T-cell clonal expansion capacity. Later, this capacity rapidly declines by more than 90% until about 50 years old.
The model was built using publicly available data on COVID-19 mortality from the Centers for Disease Control and US Census Bureau and studies on telomeres over the past two decades.
Scientists noted, “Assembling telomere length information about a person or specific demographic could help doctors know who was less susceptible. And then they could allocate resources, such as booster shots, according to which populations and individuals may be more susceptible to COVID-19.”
Co-authors include Ezra Susser, Mailman School of Public Health, Columbia University; Konstantin Arbeev and Anatoliy Yashin, Social Science Research Institute, Duke University; Daniel Levy, National Heart, Lung, and Blood Institute, National Institutes of Health; Simon Verhulst, University of Groningen, Netherlands; Abraham Aviv, New Jersey Medical School, Rutgers University.
- James J. Anderson et al. Telomere-length dependent T-cell clonal expansion: A model linking aging to COVID-19 T-cell lymphopenia and mortality. DOI: 10.1016/j.ebiom.2022.103978