Overview

• Researchers using aging-mouse models and human lung tissue linked elevated apolipoprotein D in older lungs to weaker type I interferon responses and greater influenza replication.
• Mechanistic experiments showed ApoD triggers extensive mitophagy in senescent cells, undermining mitochondrial signaling required for innate antiviral defense.
• Aged ApoD knockout mice survived otherwise lethal influenza challenges with lower lung viral loads and reduced pulmonary damage.
• Clearing senescent cells with the senolytic ABT-263 in aged mice lowered ApoD levels and eased influenza-associated lung pathology.
• The authors emphasize that findings are preclinical and recommend clinical trials of senolytics, mitophagy inhibitors, or ApoD-targeting therapies for older patients.