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 responds structurally more slowly and less powerfully, while smouldering inflammation, underlying diseases and nutritional deficiencies amplify that effect. Vaccination helps, although the protection it offers older people is smaller than in younger people.
The immune system changes structurally as we age, a phenomenon called immunosenescence. Both the first line of defence (innate immunity) and the long-term memory response (adaptive immunity) become impaired. B cells and T cells -- the cells that produce antibodies and recognise viruses -- function less effectively and also build up less protection after vaccination. This is clearly visible with influenza vaccination: older people respond less strongly than younger adults.
Alongside a weakened immune defence, many older people also experience an opposing phenomenon: inflammageing. This is a smouldering, chronic low-grade inflammation that is already present before the infection occurs. In SARS-CoV-2, this background inflammation proved to significantly disrupt the response to the virus. Notably, this pattern is not exclusive to older people. Younger people who have experienced many infections throughout their lives can have a similar immune profile.
A cellular mechanism has also been discovered that plays a specific role in influenza. As we age, the level of a protein (ApoD) rises in the lungs and blood. During influenza infection, this protein disrupts the energy factories of cells (mitochondria) and suppresses the early alarm signals the body uses to stop viruses. In mouse studies and aged human cells, this led to poorer control of infection, but whether this mechanism carries equal clinical weight in older people has not yet been directly proven.
Immune ageing is not the only explanation, however. In seriously ill older people in nursing homes, underlying heart and brain diseases and medical devices such as urinary catheters proved to be at least as important predictors of hospitalisation and death. And RSV, a virus that most people experience as a harmless cold, regularly causes serious respiratory infections in older people, partly because immunity following earlier RSV infections does not last long.
Nutritional deficiencies, which become more common as people age, can further undermine immune function. These include deficiencies in protein, vitamin A, vitamin E and vitamin B6. This evidence comes largely from animal studies and specific patient groups; how large this effect is in healthy older adults is less certain.
The claims are based on multiple studies with moderate strength of evidence (immunosenescence, inflammageing, RSV) and several more limited studies (ApoD mechanism in mice/cell culture, COVID immune-cell abnormalities in 7 patients, nutritional deficiencies largely from animal studies). No large randomised trials; the causal relationships are largely plausible but not always proven.