Age-related inflammation behind high rate of death among the elderly

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Why do older people in particular die from Sars-CoV-2? A new hypothesis sees chronic inflammation and an aged immune system as crucial factors.

A hypothesis about a link between age-related inflammation and severe trajectories of Covid-19, presented by two researchers in Science, could explain why older people are more likely to die from coronavirus infection. In their paper, Arne Akbar and Derek Gilroy of University College London share findings on the aging of the immune system on the one hand and findings on Covid-19 on the other.

According to her thesis, an inflammatory process that occurs in an infection with Sars-CoV-2, known as inflammatory ageing, by enticing T cells to indiscriminately destroy body cells, makes it more dangerous.

Normally, T cells that kill body cells only respond to antigens of the virus in those cells. However, according to Akbar and Gilroy, they can also acquire receptors from non-specific killer cells of the innate immune system through an aging process called senescence. The older you get, the more cells are senescented throughout the body. At the same time, inflammation such as that in Covid-19 causes many body cells to carry proteins that activate these receptors – especially senescent cells in the lungs. This combination may cause T-cells in the elderly to destroy lung tissue that is not infected by the virus.

Inflammation is a component of the early immune response to pathogens or damaged tissue. They arise because immune cells in the tissue react to molecules typical of pathogens or damaged tissues and release a number of signalling substances. These in turn alter the blood vessels so that fluid and immune cells activated by the inflammatory signals enter the tissue. Normally, the inflammation decreases when its cause is gone.

Older people, however, often show signs of chronic, “sterile” inflammation, which is not caused by pathogens: they permanently have a higher proportion of characteristic messenger substances such as C-reactive protein (CRP) and cytokines in the blood. Akbar and Gilroy do not consider this inflammation to be harmful per se, but point to the possibility that inflammation could have fatal interactions with infections caused by pathogens. Thus, in addition to the suspected effects on the T cells, the permanent inflammation also makes the immune response to various viruses ineffective. That’s why it might make sense to treat Covid-19 with antiviral and anti-inflammatory drugs – a suggestion that other experts have already made.

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