Good news! This could be a breakthrough!
"A nasal spray reversed brain aging and inflammation in just two doses, restoring memory and cognitive sharpness, in a Texas A&M study of mice that researchers say could reshape treatment for dementia."
"Summary: For decades, “neuroinflammaging”, the slow-burning inflammation that causes brain fog and memory decline, was considered an unavoidable part of getting older. However, a landmark study suggests the clock can be turned back.
Researchers developed a non-invasive nasal spray that uses microscopic “delivery parcels” to travel directly into the brain. With just two doses, the therapy dramatically reduced chronic inflammation, recharged cellular “power plants” (mitochondria), and restored memory and cognitive sharpness in aging models.
Key Facts
- Rapid & Lasting Results: Significant cognitive improvements were observed within weeks and, remarkably, persisted for months after only two doses.
- Universal Efficacy: Unlike many medical studies that show varying results by sex, this therapy proved equally effective in both males and females.
- Behavioral Recovery: Treated models showed a restored ability to recognize familiar objects and adapt to changes in their environment—key indicators of a healthy, functioning memory center.
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From the abstract:
"Neuroinflammaging, a moderate, chronic, and sterile inflammation in the hippocampus, contributes to age-related cognitive decline.
Neuroinflammaging comprises the activation of the nucleotide-binding domain, leucine-rich repeat family, and pyrin domain-containing 3 (NLRP3) inflammasomes, and the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway that triggers type 1 interferon (IFN-1) signalling.
Studies have shown that extracellular vesicles from human induced pluripotent stem cell-derived neural stem cells (hiPSC-NSC-EVs) contain therapeutic miRNAs that can alleviate neuroinflammation.
Therefore, this study examined the effects of late middle-aged (18-month-old) male and female C57BL6/J mice receiving two intranasal doses of hiPSC-NSC-EVs on neuroinflammaging in the hippocampus at 20.5 months of age. Compared with animals receiving vehicle treatment, the hippocampus of animals receiving hiPSC-NSC-EVs exhibited reductions in astrocyte hypertrophy, microglial clusters, and oxidative stress, along with elevated expression of antioxidant proteins and genes that maintain mitochondrial respiratory chain integrity.
Moreover, hiPSC-NSC-EVs therapy decreased the levels of various proteins involved in the activation of the NLRP3 inflammasome, p38/mitogen-activated protein kinase, cGAS-STING-IFN-1, and Janus kinase and signal transducer and activator of transcription signalling pathways.
Furthermore, in vitro assays using genetically engineered RAW cells and hiPSC-NSC-EVs, with or without targeted depletion of specific miRNAs, demonstrated that miRNA-30e-3p and miRNA-181a-5p, both present in hiPSC-NSC-EVs, can significantly inhibit the activation of the NLRP3 inflammasome and the STING pathway, respectively. Additionally, single-cell RNA sequencing conducted 7 days post-treatment revealed that hiPSC-NSC-EVs induce widespread transcriptomic changes in microglia, including increased expression of numerous genes that enhance oxidative phosphorylation and reduced expression of abundant genes that drive multiple proinflammatory signalling pathways.
These changes mediated by hiPSC-NSC-EVs were also associated with improved cognitive and memory function.
Thus, intranasal hiPSC-NSC-EVs therapy in late middle age can effectively diminish proinflammatory microglial transcriptome and signalling cascades that drive neuroinflammaging in the hippocampus, contributing to better brain function in old age."
Scientists reverse brain aging, with a nasal spray (original news release) "New therapy is turning back the clock in aging brains, healing inflammation, restoring memory and reshaping the future of brain age-related therapies."
Fig. 2 Intranasal administration of extracellular vesicles from human induced pluripotent stem cell-derived neural stem cells (hiPSC-NSC-EVs) to late middle-aged mice reduced hypertrophy of astrocytes and microglial clusters.
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