Scientists are rethinking brain aging after evidence suggests its effects may be partially reversible. A novel therapeutic strategy targets hidden inflammatory processes, showing early promise in restoring cognitive function. Credit: Shutterstock

A nasal spray using extracellular vesicles can reduce brain inflammation, restore cell function, and improve cognition, offering a potential breakthrough in reversing brain aging.

Think of the brain less like a machine that simply wears out and more like one that gradually overheats.

As people age, low-level inflammation builds up in key regions tied to memory and learning. This ongoing irritation, often called “neuroinflammaging,” has been linked to brain fog, slower thinking, and a higher risk of diseases such as Alzheimer’s. For years, scientists believed this process was unavoidable.

New research suggests otherwise.

Breakthrough Nasal Spray Reverses Brain Inflammation

A team at the Texas A&M University Naresh K. Vashisht College of Medicine has found evidence that this age-related brain inflammation may be reversible. Their approach is surprisingly simple: a nasal spray.

The study, led by Dr. Ashok Shetty along with Dr. Madhu Leelavathi Narayana and Dr. Maheedhar Kodali, introduced a treatment that delivered striking results after just two doses. The therapy reduced inflammation, restored cellular energy systems in the brain, and improved memory.

With support from the NIA, discoveries like Shetty’s highlight Texas A&M’s role as a leader in research, where global and national priorities inspire the next wave of innovation. Credit: Texas A&M University Naresh K. Vashisht College of Medicine

Rapid Results and Long-Lasting Cognitive Benefits

One of the most notable findings was the speed of the response. Improvements appeared within weeks and continued for months.

Published in the Journal of Extracellular Vesicles, the research points to a possible shift in how neurodegenerative diseases are treated and how aging in the brain is understood.

“Brain age-related diseases like dementia are a major health concern worldwide,” Shetty said. “What we’re showing is brain aging can be reversed, to help people stay mentally sharp, socially engaged and free from age-related decline.”

Implications for Dementia and Public Health

The findings could have wide-reaching implications.

“As we develop and scale this therapy, a simple, two-dose nasal spray could one day replace invasive, risky procedures or maybe even months of medication,” Shetty said.

The need for new approaches is urgent. In the United States, new dementia cases are expected to rise from about 514,000 in 2020 to roughly 1 million by 2060. “The trend signals a pressing need for policies and innovative interventions that can minimize both the risk and severity of neurodegenerative disorders like dementia,” Shetty said.

Universal Effectiveness Across Genders

The treatment also showed similar effectiveness in males and females, which is uncommon in biomedical research.

“It’s universal,” Shetty said. “Treatment outcomes were consistent and similar across both sexes.”

Researchers believe the approach could eventually help stroke survivors recover lost function or even slow or reverse cognitive decline in people.

In Shetty’s lab, researchers develop an innovative nasal spray targeting brain aging. Credit: Texas A&M University Division of Marketing and Communications

“Our approach redefines what it means to grow old,” Shetty said. “We’re aiming for successful brain aging: keeping people engaged, alert, and connected. Not just living longer, but living smarter and healthier,” Shetty said.

Extracellular Vesicles and MicroRNA Mechanism

The treatment relies on tiny biological particles called extracellular vesicles (EVs). These structures act as carriers for microRNAs, which help regulate genes and signaling pathways in the brain.

“MicroRNAs act like master regulators,” Narayana said. “They help modulate and regulate many gene and signaling pathways in the brain.”

Delivery is a key part of the process.

Intranasal Delivery: Direct Path to the Brain

When administered as a nasal spray, the EVs bypass the brain’s protective barrier and move directly into brain tissue.

“The mode of delivery is one of the most exciting aspects of our approach,” Kodali said. “Intranasal delivery allows us to reach, and treat, the brain directly without invasive procedures.”

Once inside, the microRNAs reduce activity in inflammatory systems such as the NLRP3 inflammasome and the cGAS–STING pathways.

Restoring Mitochondrial Function and Brain Energy

The therapy also improved the function of mitochondria, which supply energy to brain cells.

By restoring these systems, the treatment enhanced the brain’s ability to process and store information.

“We are giving neurons their spark back by reducing oxidative stress and reactivating the brain’s mitochondria,” Narayana said.

Dr. Ashok K. Shetty. Credit: Texas A&M University Naresh K. Vashisht College of Medicine

Behavioral testing supported these findings. Subjects that received the treatment showed better recognition of familiar objects and greater awareness of changes in their surroundings.

“We are seeing the brain’s own repair systems switch on, healing inflammation and restoring itself,” Shetty said.

Patent Progress and Translational Research Efforts

Although more research is needed, the team has already filed a U.S. patent for the therapy. The work also highlights Texas A&M’s role in advancing research that connects scientific discovery with practical treatments.

“We aren’t just trying to understand the biological mechanisms, we are translating and developing our findings into real-world therapies that could make a difference,” Shetty said.

NIA Partnership Fuels Breakthrough in Brain Aging Therapy

Support from the National Institute on Aging (NIA) helped bring together the expertise and resources needed to develop the therapy.

“Our partnership with the NIA is very important,” Shetty said. “This kind of work requires resources and the right people to tackle problems and develop solutions that could change lives.”

While aging may affect how the brain functions, researchers are now finding ways to restore its performance. This work points toward a future where cognitive decline can be slowed, or even reversed, opening the door to healthier brain aging.

Reference: “Intranasal Human NSC-Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS-STING Signalling, in Aged Hippocampus” by Leelavathi N. Madhu, Maheedhar Kodali, Shama Rao, Sahithi Attaluri, Raghavendra Upadhya, Goutham Shankar, Bing Shuai, Yogish Somayaji, Shruthi V. Ganesh, Vignesh S. Kumar, Jeswin E. James, Padmashri A. Shetty, Avery LeMaire, Xiaolan Rao, James J Cai and Ashok K. Shetty, 8 February 2026, Journal of Extracellular Vesicles.
DOI: 10.1002/jev2.70232

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