Why do older people become seriously ill from an infection more quickly?
Older people become seriously ill from infections more quickly because their immune system is less effective and a smouldering inflammation is simultaneously active. Vaccinations help, although they work slightly less well in older people than in younger ones.
The immune system wears down over the years. Both the rapid, broad first line of defence and the targeted response involving specialised cells (B and T cells) function less effectively. The result is that infections are stopped less quickly and more often develop into serious illness. This is visible with the flu vaccine: after vaccination, older people build up fewer protective antibodies than younger adults.
At the same time, many older people harbour a chronic, low-grade inflammation in the body. This phenomenon is called 'inflammaging' (a contraction of 'inflammation' and 'aging'). That persistent inflammatory activity makes the body more vulnerable when an acute infection, such as COVID-19, is added on top. How severely this plays out varies from person to person: it depends not only on chronological age, but also on someone's prior immune history.
A more specific mechanism has also been discovered that explains why older people become more severely ill from influenza. In older humans and mice, a protein called ApoD is strongly elevated. During a flu infection, ApoD triggers a kind of self-destruction process in the cell's energy factories. This suppresses precisely the signalling molecules that normally raise the alarm and slow down the virus. As a result, the virus can replicate more easily. In mouse studies, older animals proved more resistant to severe influenza when this protein was switched off or when senescent cells were cleared away.
An older study adds a caveat: part of the extra risk in older people comes not only from the ageing immune system itself, but also from comorbidities such as cardiovascular disease, neurological problems, and the use of medical devices such as a urinary catheter. This does not alter the fact that more recent research confirms immunosenescence and inflammaging as independent factors.
In practical terms, vaccination and good management of underlying conditions are the most tangible measures. For RSV, a virus that regularly causes serious respiratory complaints in older people, two vaccines are now available. Whether interventions that clear senescent cells or inhibit ApoD will ever prove useful as a therapy remains purely experimental and has not yet been studied in humans.
Based on multiple reviews and several experimental studies (mice/lab). The ApoD finding has so far only been confirmed in animal research. The claim about comorbidities as an explanation comes from a 1988 study and is partly in tension with the more recent immunological literature.