How Ageing Impairs The Antiviral Response

While COVID-19 is a disease that particularly affects the elderly, it is well established that the ability of the immune system to fend of viruses and other pathogens declines with age.

The immune system has two arms: the adaptive immune system, which recognises and mounts highly specific responses to different pathogens, and the innate immune system, the cells of which can recognise a wide range of pathogens and trigger inflammation. Both arms of the immune system decline as we age.

The adaptive immune system’s pool of naive T cells – white cells that are able to respond to newly encountered viruses – decreases with age. T cells also suffer from a reduced ability to recognise viral antigens, and reduced ability to kill infected cells. Meanwhile, antibody production by B cells is impaired, while B memory cell numbers decline, compromising immunity to previously encountered infections. Furthermore, the weakening of the adaptive immune system results in a diminished response to vaccination.

In the case of the innate immune system, dendritic cells and macrophages – cells that present viral antigens to the adaptive immune system as well as kicking off the inflammatory process – are less able to produce interferons. These proteins are important in the defence against viral pathogens, as they interfere with viral replication while boosting the activity of immune cells.

The decline of the immune system is a challenge that needs to be addressed as part of the effort to combat age-related disease. One strategy aimed at slowing the ageing of the immune system is to slow the atrophy of the thymus, the organ in which T cells undergo their ‘quality control’ and mature into naive T cells. This can be achieved using stem cell therapy, genetic reprogramming, and administration of immune signalling molecules, all of which have shown some success in rejuvenating the ageing thymus in animal models.

Another possible approach is to target telomere shortening, which is associated with reduced T cell replication. There is evidence, for example, that enhancing the activity of telomerase (the enzyme that lengthens telomeres) enhances the antiviral activity of T cells.