How Aging Increases Flu Severity

A team led by scientists from the University of Nottingham has uncovered why older individuals are more likely to suffer severe effects from influenza and how this discovery may help develop new strategies to address the risk. The findings, published in PNAS, show that aging is associated with high production of a glycosylated protein called apolipoprotein D (ApoD), which plays a role in lipid metabolism and inflammation. Compared to younger individuals, older people produce much greater levels of ApoD during infection, and this disrupts the body’s ability to resist viruses, leading to more serious outcomes.

The research team demonstrated that elevated ApoD production in the lungs of older individuals drives tissue damage and reduces the protective antiviral response of type I interferons. These proteins are normally critical for controlling viral replication and providing an early defense against infection. By impairing this pathway, higher ApoD levels create conditions that allow influenza to cause more extensive disease in the elderly.

The collaborative study used an aging-mouse model and appropriate donor human tissue sections to identify ApoD as a key age-related factor that interferes with proper immune activation by promoting mitochondrial breakdown, known as mitophagy. Mitochondria are essential for providing cellular energy and for triggering interferon production, both of which are important in antiviral defense. The disruption of this process results in increased viral replication and heightened lung injury during influenza infection.

Co-author Kin-Chow Chang from the University of Nottingham explained the significance, of the study stating: “Aging is a leading risk factor in influenza-related deaths. Furthermore, the global population is aging at an unprecedented rate in human history, posing major issues for healthcare and the economy. So we need to find out why older patients often suffer more severely from influenza virus infection.”

Building on these insights, the study suggests that ApoD could become a valuable target for therapeutic development. By inhibiting ApoD activity, it may be possible to lessen the severity of influenza in older adults, reducing both illness and death.