Description
Inflammaging is the increased state of inflammation associated with aging. Several inflammatory pathways are upregulated during normal aging, including the nuclear factor kappa-B (NF-κB) pathway. Activation of this pathway leads to the increase in pro-inflammatory cytokine production that is characteristic of inflammaging. Antioxidant pathways, such as nuclear factor E2-related factor 2 (Nrf2), are also impaired with aging. Acetylcholine (ACh) is a neurotransmitter that acts primarily in the central nervous system but has other effects throughout the body. Previous studies have explored the anti-inflammatory effects of acetylcholine in the lungs and spleen. Acetylcholine signaling effects the activation of many pathways, including inhibition of the pro-inflammatory NF-κB pathway and increased activation of the antioxidant Nrf2 pathway. Donepezil is a drug used to treat Alzheimer’s Disease. It increases the amount of available acetylcholine by blocking the enzyme acetylcholinesterase. This study investigates the effects of increasing acetylcholine via donepezil on inflammaging of the lungs and spleen in a murine model. Donepezil treatment in our aged mouse model did not significantly change the expression of cytokine genes. We found noticeable differences in the extent of inflammaging between males and females, as well as between the lungs and spleen. One major consequence of inflammaging is decreased immunity. In the elderly, this results in increased risk of death from respiratory viral infections such as influenza and SARS-CoV2. Influenza virus effects many lives every year and causes death in the elderly population. Aging impairs the body’s ability to fight infection and there are limited interventions for viral infection. The available antivirals can be overcome by viral mutations, which occur frequently. There is a need for therapeutics that target cellular pathways to help fight infection. Increasing acetylcholine levels with donepezil administration during viral infection with influenza A in vitro showed the potential to decrease inflammation. This study explores the potential anti-inflammaging properties of donepezil and suggests that increasing acetylcholine may decrease inflammation caused by influenza virus infection.
