Aging has long been known to take its toll on our brains, particularly in the hippocampus, a region crucial for learning and memory. Researchers at the University of California San Francisco (UCSF) have made a groundbreaking discovery that sheds new light on this process. By examining how genes and proteins change over time in mice, they identified a protein called FTL1 as the key culprit behind brain aging.

Old mice with higher levels of FTL1 exhibited fewer connections between brain cells in the hippocampus and diminished cognitive abilities. In experiments, artificially increasing FTL1 levels in young mice led to changes in their brains and behavior that resembled those of older mice. Furthermore, when scientists reduced FTL1 levels in old mice, they observed a reversal of impairments – regaining more connections between nerve cells and improved memory test results.

One of the most intriguing findings was that high levels of FTL1 slowed down metabolism in hippocampal cells. However, treating these cells with a compound that stimulates metabolism prevented this effect. This suggests that targeting FTL1 could be a potential therapeutic strategy for alleviating the consequences of brain aging.

“We’re seeing more opportunities to alleviate the worst consequences of old age,” said Saul Villeda, PhD, associate director of the UCSF Bakar Aging Research Institute and senior author of the paper. “It’s a hopeful time to be working on the biology of aging.” The researchers’ optimism is well-founded, as this discovery could pave the way for new therapies that block the effects of FTL1 in the brain.

This study was funded by several organizations, including the Simons Foundation, Bakar Family Foundation, and National Science Foundation. As research continues to unfold, it’s essential to remember that understanding brain aging is crucial for developing effective treatments and improving overall health and well-being.

Scientists have made a groundbreaking discovery that could potentially reverse memory loss associated with neurodegenerative diseases. Researchers from Inserm and the University of Bordeaux, in collaboration with colleagues from the Université de Moncton in Canada, have successfully established a causal link between mitochondrial dysfunction and cognitive symptoms related to these conditions.

Mitochondria are tiny energy-producing structures within cells that provide the power needed for proper functioning. The brain is one of the most energy-demanding organs, relying on mitochondria to produce energy for neurons to communicate with each other. When mitochondrial activity is impaired, neurons fail to function correctly, leading to progressive neuronal degeneration and eventually, cell death.

In Alzheimer’s disease, for example, it has been observed that impaired mitochondrial activity precedes neuronal degeneration and ultimately, leads to memory loss. However, due to the lack of suitable tools, researchers were unable to determine whether mitochondrial alterations played a causal role in these conditions or were simply a consequence of the pathophysiological process.

In this pioneering study, researchers developed a unique tool that temporarily stimulates mitochondrial activity. By activating G proteins directly in mitochondria using an artificial receptor called mitoDreadd-Gs, they successfully restored both mitochondrial activity and memory performance in dementia mouse models.

“This work is the first to establish a cause-and-effect link between mitochondrial dysfunction and symptoms related to neurodegenerative diseases,” explains Giovanni Marsicano, Inserm research director. “Impaired mitochondrial activity could be at the origin of the onset of neuronal degeneration.”

The tool developed by researchers has opened doors to considering mitochondria as a new therapeutic target for treating memory loss associated with neurodegenerative diseases. Further studies are needed to measure the effects of continuous stimulation of mitochondrial activity and determine its potential impact on symptoms and neuronal loss.

Ultimately, this research holds promise for identifying molecular and cellular mechanisms responsible for dementia, facilitating the development of effective therapeutic targets, and potentially delaying or even preventing memory loss associated with neurodegenerative diseases.

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Alzheimer’s risk may start at the brain’s border, not inside it

The brain’s health depends on more than just its neurons. A complex network of blood vessels and immune cells acts as the brain’s dedicated guardians – controlling what enters, cleaning up waste, and protecting it from threats by forming the blood-brain barrier.

A new study from Gladstone Institutes and UC San Francisco (UCSF) reveals that many genetic risk factors for neurological diseases like Alzheimer’s and stroke exert their effects within these very guardian cells.

“When studying diseases affecting the brain, most research has focused on its resident neurons,” says Gladstone Investigator Andrew C. Yang, PhD, senior author of the new study. “I hope our findings lead to more interest in the cells forming the brain’s borders, which might actually take center stage in diseases like Alzheimer’s.”
The findings, published in Neuron, address a long-standing question about where genetic risk begins and suggest that vulnerabilities in the brain’s defense system may be a key trigger for disease.

For years, large-scale genetic studies have linked dozens of DNA variants to a higher risk of neurological diseases like Alzheimer’s, Parkinson’s, or multiple sclerosis. Yet, a major mystery has persisted: over 90% of these variants lie not in the genes themselves, but in the surrounding DNA that does not contain the code for making proteins, once dismissed as “junk DNA.”

These regions act as complex dimmer switches, turning genes on or off. Until now, scientists haven’t had a full map of which switches control which genes or in which specific brain cells they operate, hindering the path from genetic discovery to new treatments.

A New Technology Finds Answers

The blood-brain barrier is the brain’s frontline defense – a cellular border made up of blood vessel cells, immune cells, and other supporting cells that meticulously controls access to the brain. Yet, these important cells have been difficult to study, even using the field’s most powerful genetic techniques.

To overcome this, the Gladstone team developed MultiVINE-seq, a technology that allows for the simultaneous analysis of multiple genomic and transcriptomic datasets from individual cells.

The new study utilized this technology to investigate the role of immune cells in the brain’s defense system. The researchers found that certain genetic variants associated with Alzheimer’s disease were more prevalent in immune cells than in neurons or other brain cells.

This suggests that the brain’s guardian cells may play a crucial role in the development and progression of Alzheimer’s disease.
The study also identified a potential new target for treating Alzheimer’s disease: PTK2B, a protein that is involved in the regulation of immune cell activity. The researchers found that therapies targeting PTK2B are already being developed for cancer treatment, and could potentially be repurposed for Alzheimer’s disease.

Location, Location, Location

The study’s findings on the brain’s “guardian” cells point to two new opportunities for protecting the brain. Located at the critical interface between the brain and the body, the cells are continually influenced by lifestyle and environmental exposures, which could synergize with genetic predispositions to drive disease.

Their location also makes them a promising target for future therapies, potentially allowing for drugs that can bolster the brain’s defenses from the “outside” without needing to cross the formidable blood-brain barrier. This work brings the brain’s vascular and immune cells into the spotlight, and could inform new, more accessible drug targets and lifestyle interventions to protect the brain from the outside in.

About the Study

The study, “Human brain vascular multi-omics elucidates disease risk associations,” was published in the journal Neuron on July 28, 2025. The work was supported by several funding agencies, including the National Institute of Neurological Disorders and Stroke, Alzheimer’s Association, BrightFocus Foundation, Cure Alzheimer’s Fund, Ludwig Family Foundation, Dolby Family Fund, Bakar Aging Research Institute, National Institute of Mental Health, National Institute of Aging, Leducq Foundation, and Joachim Herz Foundation.