Great if it works
Edited by Gaby Clark, reviewed by Robert Egan
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Scientists call this slow burn "neuroinflammaging," and for decades it was thought to
be the inevitable price of growing older. Until now.
A landmark study by researchers at Texas A&M University
Naresh K. Vashisht College of Medicine suggests the inflammatory tide
responsible for brain aging and brain fog might actually be reversible. And the
solution doesn't involve brain surgery, but a simple nasal spray.
Led by Dr. Ashok Shetty, university distinguished professor
and associate director of the Institute for Regenerative Medicine, along with
senior research scientists Dr. Madhu Leelavathi Narayana and Dr. Maheedhar
Kodali, the team developed a nasal spray that, with just two doses,
dramatically reduced brain inflammation, restored the brain's cellular power
plants and significantly improved memory.
The most surprising part? It all happened within weeks and
lasted for months.
The findings, published in the Journal of Extracellular Vesicles, could reshape the future
of neurodegenerative therapies and may even change how scientists think about
brain aging itself.
"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."
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
Brain fog to brain focus, the future of cognitive therapy
The implications of this research could be nothing short of
revolutionary.
"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 societal impact could be just as profound. In the United
States alone, new dementia cases are projected to double over the next four
decades, from about 514,000 in 2020 to about 1 million in 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.
The study also hints at broad applicability, working equally
effectively across both genders—a rare outcome in biomedical research.
"It's universal," Shetty said. "Treatment
outcomes were consistent and similar across both sexes."
One day, the approach could even help stroke survivors
rebuild lost brain function, or slow—even reverse—the effects of cognitive
aging in humans.
"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.
Dr. Ashok K. Shetty University Distinguished Professor Texas
A&M University Naresh K. Vashisht College of Medicine. Credit: Texas
A&M University
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Rewiring the brain from the inside out
At the heart of this groundbreaking development are millions
of microscopic biological parcels known as extracellular vesicles (EVs). They
act like delivery vehicles, carrying powerful genetic cargo called microRNAs.
"MicroRNAs act like master regulators," Narayana
said. "They help modulate and regulate many gene and signaling pathways in
the brain."
But the delivery route is just as important as the cargo.
Packed into a nasal spray, the tiny EVs bypass the brain's protective
shield and travel directly into brain tissue, where they are absorbed.
"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 absorbed into the brain's resident immune cells, the
microRNAs suppress systems, like NLRP3 inflammasome and the cGAS–STING signaling
pathways, known to drive chronic inflammation in aging brains.
At a cellular level, the treatment recharged neuronal
mitochondria, or the power plants that live inside the brain's cells.
By recharging these cellular power plants, the therapy
didn't just clear brain fog, it physically improved 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.
Behavioral tests confirmed the biology. Models treated
with the nasal spray showed remarkable improvements in not only recognizing
familiar objects but also detecting new objects and changes in their
environment, a sharp contrast to the control.
"We are seeing the brain's own repair systems switch
on, healing inflammation and restoring itself," Shetty said.
While further research is needed, Shetty and his team have
already filed a U.S. patent for the therapy, marking a milestone in what could
become a breakthrough for brain aging treatments.
Behind the breakthrough
Breakthroughs like the one led by Shetty highlight Texas
A&M as a research powerhouse, where national and global research priorities
help shape the next generation of innovative solutions.
"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.
Backed by the National Institute on Aging (NIA), the Texas
A&M team pooled collaborative knowledge, expertise and resources to turn a
simple nasal spray into a therapy with the potential to reframe how scientists
think about brain aging.
"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."
Ultimately, while the brain's engine may sputter with age,
scientists are now learning how to reignite it, sparking a new era of cognitive
health and showing that the clock on brain aging might not just be paused, it
can be turned back.
More information
Leelavathi N. Madhu et al, Intranasal Human NSC‐Derived
EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and
cGAS‐STING
Signalling, in Aged Hippocampus, Journal
of Extracellular Vesicles (2026). DOI:
10.1002/jev2.70232