The immune system gets poorer as people age

With aging, the immune system works worse. It becomes more susceptible to infections and vaccines no longer work as effectively. People as they age exhibit a general decline in adaptive immune function, with important implications for health and life expectancy.

Previous studies have found a widespread loss of the diversity of the immune repertoire in human peripheral blood during aging; however, little is known about the aging of the repertoire in other immune compartments or in species other than humans.

The effectiveness of the immune system is based on its ability to generate an enormous variety of different antibody sequences, with a correspondingly wide range of antigenic specificities, and to progressively adjust the composition of this antibody population in response to antigen exposure. In humans, antibody repertoire sequencing has uncovered a number of important age-related changes, including a reduced number of clones and unique sequences, increased reference mutation, more frequent and larger clonal expansions, altered B cell selection, and a change towards memory. compartment. While the diversity of the repertoire within individuals decreases with age, the variability between individuals increases, and the repertoires of older individuals differ more from each other than those of young individuals.

A research team led by Darío Riccardo Valenzano from the Max Planck Institute of Biology for Aging in Cologne, Germany, worked around this problem, investigated whether short-lived killifish suffer from aging immune system. In fact, they found that as early as four months of age, they have less diverse circulating antibodies compared to younger fish, which may contribute to a general decrease in immune function. His findings are published in the specialized journal eLife Sciences Publication.

The immune system must constantly respond to new pathogen attacks and remember them to be protected during the next infection. For this purpose, B-cells build a repository of information and produce a variety of antibodies that can directly recognize pathogens. “We wanted to know about the repertoire of antibodies in old age,” explains Valenzano, who led the research. It is difficult to study the immune system of a human being throughout their lives because they live a long time. In addition, antibodies can only be studied in peripheral blood, since it is problematic to obtain samples from other tissues. That's why we use the killis. They are fish that have a very short life and we can obtain samples of different tissues.” Killis are the shortest lived vertebrates that can be maintained in a laboratory. They live only three to four months, age in a short time and have become the focus of research on aging in recent years because of these characteristics.

Scientists conducted the first experiments in sequencing the immunological repertoire in this species, demonstrating that adult killis express chain repertoires and individualized that they experience rapid loss of diversity with age. “By sequencing the repertoires of isolated intestinal samples, we further found that the intestinal antibody repertoire of the killites exhibits a much more dramatic age-dependent loss of diversity than the body as a whole, possibly due to a much higher prevalence of clones expanded in the intestine, and that this loss of diversity is associated with changes in gene expression that indicate a reduced activity of B cells,” said the specialist.

The researchers were able to characterize with great precision all the antibodies that the killites produce. They found that older ones have different types of antibodies in their blood than younger fish. They also had a lower diversity of antibodies throughout the body. “If we have fewer different antibodies as we age, this could lead to a reduced ability to respond to infections. Now we want to investigate further why B cells lose their ability to produce various antibodies and whether it is possible for them to rejuvenate and thus regain this ability”, concludes Valenzano.

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