Scientists have revealed why influenza infections are often more dangerous in older adults, and their discovery opens the door to new treatments that could reduce this heightened risk. The research, published in PNAS, identifies a key biological factor that makes elderly patients more vulnerable to severe outcomes when infected with the flu virus.
The study found that older people produce much higher levels of apolipoprotein D (ApoD), a glycosylated protein involved in lipid metabolism and inflammation. While ApoD is a natural part of cellular processes, in excess, it appears to weaken the body’s defences against viral infection. This overproduction reduces the ability of older patients to mount an effective immune response, making influenza both more severe and more damaging.
Researchers showed that increased ApoD in the lungs leads to extensive tissue injury during infection. This damage undermines the body’s antiviral type I interferon response, which usually helps to contain viruses. Without this protective response, influenza infection spreads more easily and becomes more destructive, particularly in the ageing lung.
An international team of scientists from the China Agricultural University, the University of Nottingham, the Institute of Microbiology at the Chinese Academy of Sciences, the National Institute for Viral Disease Control and Prevention at the Chinese Centre for Disease Control and Prevention, and the University of Edinburgh conducted the investigation. According to Professor Kin-Chow Chang, from the School of Veterinary Medicine and Science at the University of Nottingham, “Ageing is a leading risk factor in influenza-related deaths. With global populations ageing at an unprecedented pace, understanding why older patients experience worse outcomes is crucial for healthcare and the wider economy.”
Using an ageing mouse model alongside carefully selected human tissue samples, the team investigated the mechanisms driving this age-related vulnerability. They discovered that ApoD impairs the activation of the immune system by accelerating the breakdown of mitochondria, a process known as mitophagy. Since mitochondria are essential both for producing cellular energy and for triggering protective interferons, their loss allows the virus to replicate more freely, resulting in higher viral loads and greater lung damage.
These findings identify ApoD as a critical therapeutic target. By inhibiting its harmful effects, researchers hope to develop treatments that strengthen the immune response in older patients and prevent severe influenza outcomes. As Professor Chang explained, “There is now an exciting opportunity to improve outcomes for the elderly by targeting ApoD, potentially reducing morbidity and mortality linked to influenza worldwide.”
More information: Kin-Chow Chang et al, ApoD mediates age-associated increase in vulnerability to influenza virus infection, Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2423973122
Journal information: Proceedings of the National Academy of Sciences Provided by University of Nottingham
