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"Jaw-dropping" breakthrough as scientists reverse aging by decades

Scientists have made a “jaw-dropping” breakthrough in aging research. The experts have successfully reversed brain aging in mice by years, if not decades. 

In a remarkable convergence, scientists have discovered that the same blood factor is responsible for the cognitive enhancement that is associated with exercise, young blood transfusion, and the longevity hormone klotho.

This stunning revelation is the result of three studies from the University of California, San Francisco (UCSF) and the University of Queensland in Australia.

Incredible transformation 

The transformation observed in the laboratory mice was attributed to PF4, a protein that is naturally present in the bloodstream. 

When administered to older mice, the scientists observed a restoration of cognitive sharpness comparable to their middle age. Among younger mice, the protein substantially boosted their intelligence.

The researchers gauged the impacts of PF4 on older mice, about two years old, which can be equated to a human age of approximately 70 years. Astonishingly, the cognitive faculties of these mice were rejuvenated to levels equivalent to 30 or 40-year-old humans.

The role of PF4 in reversed aging

Inflammation is a key contributor to both brain and body aging. It appears that PF4 plays a crucial role in mitigating inflammation by modulating the immune response.

The researchers used multiple strategies to introduce more PF4 into the body. These included blood transfusions from younger to older mice, physical exercise, and intriguingly, the influence of klotho, a gene intricately involved in the aging trajectory.

Brain rejuvenation 

Study senior author Saul Villeda is the associate director at the UCSF Bakar Aging Research Institute.

“Young blood, klotho, and exercise can somehow tell your brain, ‘Hey, improve your function.’ With PF4, we’re starting to understand the vocabulary behind this rejuvenation,” said Villeda.

Further research is needed 

As with any scientific breakthrough, further research is needed. Questions remain, especially concerning the potential repercussions of manipulating the immune system in such a manner. This includes possible implications for our disease-fighting capabilities.

Still yet, the studies have revealed remarkable insights. In one study, mice that received PF4 injections demonstrated reversed aging and improved brain function. This was attributed to a subdued immune response in their brains and bodies. This resulted in better memory and learning outcomes.

Pro-aging immune factors

“PF4 actually causes the immune system to look younger; it’s decreasing all of these active pro-aging immune factors, leading to a brain with less inflammation, more plasticity, and eventually more cognition,” said Villeda.

“We’re taking 22-month-old mice, equivalent to a human in their 70s, and PF4 is bringing them back to function close to their late 30s, early 40s.”

Another study showed that the introduction of klotho spurred the body to produce more PF4. This had profound effects on reversed aging in the brain, particularly the regions governing memory creation.

Tara Walker was the lead author of the study from the University of Queensland. She found that platelets released PF4 into the bloodstream following exercise. When she tested PF4 on its own, as Dubal and Villeda also had, it improved cognition in old animals. 

Remarkable alignment

The remarkable alignment of these discoveries was emphasized by Dr. Dena Dubal, a neurology professor at UCSF. 

“When we realized we had independently and serendipitously found the same thing, our jaws dropped. The fact that three separate interventions converged on platelet factors truly highlights the validity and reproducibility of this biology,” said Dr. Dubai. “The time has come to pursue platelet factors in brain health and cognitive enhancement.”

“For a lot of people with health conditions, mobility issues or of advanced age, exercise isn’t possible, so pharmacological intervention is an important area of research,” said Walker. “We can now target platelets to promote neurogenesis, enhance cognition and counteract age-related cognitive decline.” 

The studies are published in the journals Nature, Nature Aging, and Nature Communications.

More about PF4 

PF4, or Platelet Factor 4, is a small cytokine belonging to the CXC chemokine family that is primarily associated with platelets. While the studies were focused on its potential in reversing the signs of aging in the brain, PF4 is more commonly known for other functions.

Origin and structure

PF4 is produced by platelets and stored in their alpha granules. It is released in large quantities upon platelet activation.

Role in coagulation

PF4 plays a role in blood coagulation and formation of blood clots. It can bind to heparin, neutralizing its anticoagulant effects. This property has clinical significance, especially in conditions like heparin-induced thrombocytopenia (HIT). 

In HIT, the complex formed by heparin and PF4 can lead to platelet activation, resulting in clot formation in the blood vessels.

Immune modulation

PF4 is chemotactic for neutrophils and monocytes, meaning it can attract these immune cells to sites of injury or inflammation. This makes it an essential player in the body’s immune response.

Interaction with tumors

Some studies have indicated that PF4 might have an inhibitory effect on tumor growth. It has been suggested that the protein might inhibit angiogenesis (formation of new blood vessels) which is crucial for the growth of tumors.

Potential therapeutic uses

Beyond the research on brain aging, PF4 has been looked at for various therapeutic uses, including as a potential agent to inhibit angiogenesis in tumors, and as a marker to detect and diagnose conditions like HIT.


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