A novel nasal spray-based approach to deliver therapeutic miRNA-laden extracellular vesicles could combat neuroinflammaging and the decline of aging brains. Researchers at the Texas A&M University Naresh K. Vashisht College of Medicine (TX, USA), led by Ashok Shetty, have developed a nasal spray that delivers therapeutic miRNA encapsulated in extracellular vesicles (EVs) to the brain, effectively dampening neuroinflammation in a mouse model. The team believes that this method could be used to combat the rising prevalence of dementia, improving health spans globally. The well-worn idiom of the brain as an exceptionally high-powered computer bears more truth than its users often realize. Alongside its impressive computational power, the brain also experiences its own form of overheating, as small sections of inflammation arise and smolder in the hippocampus as we age, in a process known as neuroinflammaging. With the hippocampus being a key memory center of the brain, it is unsurprising that neuroinflammaging contributes to age-related cognitive decline and increases Alzheimer’s and dementia risk, increasingly prevalent disease areas globally. The two key components of neuroinflammaging are the activation of NLRP3 (nucleotide-binding domain, leucine-rich repeat family, and pyrin domain-containing 3) inflammasomes and the cGAS–STING (cyclic GMP-AMP synthase–stimulator of interferon genes) pathway, which triggers type-1 interferon signaling. Previous studies have identified that EVs isolated from human iPSC-derived neural stem cells (hiPSC-NSC-EVs) contain miRNAs that can dampen neuroinflammation through the inhibition of the NLRP3 inflammasomes and the cGAS–STING pathway. Using this information, the team developed a nasal spray containing hiPSC-NSC-EVs, which they administered in two…