Why the Flu Can be Deadly for Older People, and How Researchers Discovered the Cause

Scientists have discovered why older people are more likely to develop severe cases of influenza and can now use their findings to counteract this risk.

Apolipoprotein D and Influenza

In fact, it has been found that older people produce a glycosylated protein called apolipoprotein D (ApoD), which is involved in fat metabolism and inflammation, in much higher quantities than younger people. This reduces the patient’s resistance to viral infections, leading to a more severe course of the disease.

The team found that a sharp increase in ApoD production in the lungs with age leads to extensive tissue damage during infection, reducing the protective antiviral type I interferon response. The research was an international collaboration led by scientists from China Agricultural University, the University of Nottingham, the Institute of Microbiology (Chinese Academy of Sciences), the National Institute for Virus Control and Prevention (Chinese Center for Disease Control and Prevention), and the University of Edinburgh.

“Age is a leading risk factor for deaths related to influenza. In addition, the world’s population is aging at a rate unprecedented in human history, posing major challenges for healthcare and the economy. So we need to find out why older patients often suffer more severely from influenza virus infection,” said Professor Kin-Chow Chang of the University of Nottingham’s School of Veterinary Medicine and Science and co-author of the study.

In this new study, the team investigated the mechanisms behind the increasing severity of influenza virus infections with age using an aging mouse model and appropriate human tissue sections from donors. They identified ApoD as an age-related cellular factor that impairs the activation of the immune system‘s antiviral response to influenza virus infections by causing extensive mitochondrial degradation (mitophagy), leading to increased virus production and lung damage during infection. Mitochondria are essential for cellular energy production and the induction of protective interferons.

ApoD is therefore a target for therapeutic interventions to protect against severe influenza virus infections in older people, which would have a major impact on reducing morbidity and mortality in the aging population. Professor Chang added, “There is now a promising opportunity to therapeutically improve the severity of influenza virus infections in older people by inhibiting ApoD.”