PF4 Can Improve Cognitive Function in the Aging Brain

• Scientists have uncovered potential benefits of platelet factor 4 (PF4), a type of blood factor, for enhancing cognitive function.

• This type of blood cell may be just as effective as the longevity hormone, klotho, young blood transfusions, and exercise in rejuvenating brain health. 

• PF4 has a de-aging capacity for immune cells, reducing inflammation in the brain, and boosting function.

This article was posted by ScienceDaily: 

Across three independent studies on young blood, klotho, and exercise respectively, scientists discovered a common denominator in platelet factor 4 (PF4) for improving brain function. Dena Dubal, MD, PhD, UCSF professor, and lead on the klotho study published in Nature Aging explained:  "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.  

The studies published in Nature, Nature Aging, and Nature Communications are setting the stage for alternate possibilities to promote longevity in human cells. This research aimed to understand how young blood, klotho, and exercise can improve brain function. 

What do We Know About PF4? 

Platelet factor 4 is a small chemokine protein produced by platelets. This blood factor performs many functions, most commonly promoting blood coagulation, as well as immunological protection against infections. 

As recent studies show, this blood factor also holds the potential to elongate life in humans. 

In 2014, when Saul Villeda, Ph.D., associate director of the UCSF Bakar Aging Research Institute and the senior author of the Nature paper, led the study on the impact of young blood transfusions, he discovered that injected plasma (blood without red blood cells) mimicked a process called parabiosis where two animals are linked together by their blood circulation. In parabiosis, younger animals serve almost as a life force for older counterparts, making the latter more youthful and resilient while opening the aged brain for better learning opportunities. There was just one question, how was this happening from plasma alone? 

Villeda and his team found their answer in the blood factor, PF4. Upon examining plasma material, samples of younger animals were found to contain more of the blood factor than older subjects. Simply injecting the latter with PF4 has similar benefits with young plasma, strengthening memory and learning tasks for older animals. 

According to Villeda: “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”. On its direct effects in animals, he added: “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." 

How can PF4 Improve Brain Function? 

Researchers observing klotho’s effects on brain function pieced together P4F’s potential impact on enhancing cognitive ability.  

Like young blood, klotho also draws from the benefits of PF4 for cognitive enhancement. This discovery was made a decade ago by Dena Dubal, MD, PhD, UCSF professor who showed that klotho enhances cognition in young and old animals, while simultaneously protecting the brain against age-related decline. 

Klotho’s star power comes from its unique, longevity-promoting prospects. This gene regulates oxidative stress—a process where free radicals damage cells plus DNA and fast-track aging. Klotho also stimulates growth, and performs anti-inflammatory functions linked to lifetime extension. 

Only, to understand how this hormone achieved this, the experts realized klotho had an indirect effect as its molecules never directly interacted with the brain when injected into the body—enter PF4. 

Dubal’s team uncovered that this blood factor was released by platelets after klotho was administered to the body. PF4 enhances the formation of new neural networks in the hippocampus—the region of the brain responsible for making memories. According to Dubal, “there’s room to go even in young brains to improve cognitive function."

And if exercise wasn’t already at the top of the list for maintaining physical and emotional health, regular workouts can keep the mind sharp for decades, greatly improving mental well-being. 

Tara Walker, who led the study on exercise published in Nature Communications, also found that platelets discharge PF4 into the bloodstream following exercise. 

Consistently getting your body up and moving can increase platelet count thanks to the increase in blood cells caused by physical activity. Exercise also prompts platelet release in the liver, lungs, and spleen. 

How to Increase Your Body’s Supply of PF4 

To keep your body’s supply of PF4 steady, regular exercise should be a top priority. But where advanced age or other issues make this a challenge, there are other options to raise levels of this blood factor: 

A healthy diet 

Because PF4 is released by platelets, your game plan to increase levels of this blood factor should include foods to stimulate the latter’s production. 

To achieve this, consume a diet rich in leafy vegetables like spinach. These greens are high in folate or vitamin B9 which are key nutrients for platelet release, plus red and white blood cell manufacture. 

Other foods like collard greens are high sources of Vitamin K, a core nutrient for blood clotting that can also raise your levels of PF4. As an added treat, you can indulge in some dark chocolate to enjoy the iron benefits which are a core feature for forming large cells in the bone marrow that generate platelets. 

Pharmaceutical Interventions 

Dietary supplements can also provide the right support to encourage platelet production in the bone marrow. 

Papaya leaf extract has been repeatedly studied for its potential to increase platelet count, with papaya leaf syrup recognized for its ability to increase platelet levels. 

Papaya leaf is believed to increase gene activity necessary for producing platelets and has been observed to prevent complications of thrombocytopenia, or low platelet count.  

Interventions like Recombinant Human Thrombopoietin (rhTPO) stimulate the production of megakaryocytes which are bone marrow cells, to boost platelet production. Likewise, the Romiplostim injection is commonly used to manage cases of low platelet count. 

But while these remedies are commonly administered to stimulate low platelet production, pharmaceutical options to encourage platelet and PF4 production must be under the advice and guidance of a healthcare professional. 

Conclusion 

Sometimes, the secret to a long life is already inside you. Platelet Factor 4 can support your efforts to live a long and healthy life. While research remains underway to understand how this blood factor promotes longevity, making healthy adjustments like regular exercise and eating healthy can promote PF4 production. 

References:

Lapchak PH, Ioannou A, Rani P, et al. The role of platelet factor 4 in local and remote tissue damage in a mouse model. PLoS One. 2012;7(7):e39934. doi:10.1371/journal.pone.0039934 

de Souza Pacheco AP, Goncalves M. Klotho: its various functions and association with subphenotypes. Rev Bras Hematol Hemoter. 2014;36(6):430-436. doi:10.1016/j.bjhh.2014.07.022 

Barale C, Melchionda E, Tempesta G, Morotti A, Russo I. Impact of Physical Exercise on Platelets: Focus on Its Effects in Metabolic Chronic Diseases. Antioxidants (Basel). 2023;12(8):1609. Published 2023 Aug 14. doi:10.3390/antiox12081609 

National Institutes of Health. Folate-Fact Sheet for Health Professionals  

National Institutes of Health. Vitamin K—Health Professional Fact Sheet  

National Institutes of Health. Iron—Fact Sheet for Health Professionals 

Singh SP, Kumar S, Mathan SV, et al. Therapeutic application of Carica papaya leaf extract in the management of human diseases. Daru. 2020;28(2):735-744. doi:10.1007/s40199-020-00348-7  

Wang H, Dong Q, Fu R, et al. Recombinant human thrombopoietin treatment promotes hematopoiesis recovery in patients with severe aplastic receiving immunosuppressive therapy. Biomed Res Int. 2015;2015:597293. doi:10.1155/2015/597293