MAR 30, 2022

Killifish Research Model Shows Antibody Diversity Declines with Age

WRITTEN BY: Carmen Leitch

Like other parts of our bodies, the immune system starts to wear out as we get older, and it can't fight infections as efficiently. Routine vaccinations, like the flu shot, also don't trigger as robust a response compared to what happens in younger people. Scientists have been learning more about the aging immune system, in part to find ways to boost its function.

Scientists have now revealed a new research model to study aging in the immune system: a fish with a short lifespan, known as a killifish. Data from this model have now been reported in eLife. When these fish reach four months of age, their immune system starts to show signs of aging. By then, the circulating antibodies carried by these animals are less diverse compared to younger killifish. The study authors noted that this could be one reason why the immune system is not as good at fighting infection in elderly people.

In this study, the researchers were interested in how "the antibody repertoire" might begin to decline in older organisms, said study leader Dario Riccardo Valenzano. Such a study would be extremely challenging to perform over the lifespan of a person, in part because we live for so long, explained Valenzano. Tissue samples are very hard to obtain as well, so researchers tend to focus on the antibodies that can be observed in the peripheral blood of humans. "For this reason, we used the killifish. It is very short-lived and we can get probes from different tissues."

Since killifish only live for three to four months, they are easy to raise in the laboratory and are gaining popularity in the field of aging research. Fish are also typically much easier to mate and feed compared to mice.

The world is full of microbes, and organisms from killifish to people have to fend off attacks from microbial pathogens all the time. The immune system also has ways of remembering past encounters with attackers so they are easier to fight if they're encountered again. B cells can help generate antibodies that recognize pathogens and stop their attack.

In this research, the investigators also characterized all of the antibodies generated by killifish. This reveled that the antibodies carried by older killifish are of a different type and less diverse than younger killifish.

If we lose antibodies as we age, we might not be as good at fighting infections. "We now want to further investigate why the B cells lose their ability to produce diverse antibodies and whether they can possibly be rejuvenated in the killifish and thus regain this ability," noted Valenzano.

Sources: Max Planck Institute for Biology of Ageing, eLife