2023-08-17 12:15:00
Turning back time, rewinding the tape of the aging brain. At the age of 70, you come back as clear-headed as you were at 30-40. A dream that could find an ally closer than you think: an ‘elixir’ could in fact be hidden in the blood, the explanation why both physical exercise and the longevity hormone ‘klotho’ and a blood transfusion ‘young’ appear to be able to bring cognitive improvement. The key to success? Three different studies all point in the same direction: the PF4 factor. Two groups of US researchers (both Ucsf, University of California San Francisco) and one Australian (University of Queensland) turn the spotlight on this product of platelets, in three articles that appeared in ‘Nature’, ‘Nature Aging’ and ‘Nature Communications’ .
PF4, the authors point out, is the common thread linking the various interventions examined. Platelets are a type of blood cell that alert the immune system to an injury and help blood clot. Now it turns out that platelet factor 4 (Pf4) is also a cognitive enhancer. Under its influence, old mice regain their midlife wit and young mice become more intelligent, experts say.
“It appears that young blood, protein ‘klotho and exercise can somehow tell the brain: improve your function. With PF4, we are starting to understand the vocabulary behind this rejuvenation,” highlights Saul Villeda of the ‘Ucsf Bakar Aging Research Institute, senior author of the Nature paper. Villeda led the young blood study. Dena Dubal, a UCSF professor, led the Klotho study, published in Nature Aging, and Tara Walker, a neuroscience professor at the University of Queensland led the exercise study, published in ‘Nature Communications’. “When we realized that we had independently and serendipitously found the same thing, our jaws dropped,” Dubal said. “The fact that three separate interventions converged on platelet factors highlights the validity and reproducibility of this biology. The time has come to go down this road in the field of brain health and cognitive enhancement.”
The first point of view that is offered is that of Villeda’s team, who in 2014 had discovered that the blood plasma of young people injected into elderly animals had a restorative effect. When his team compared the young plasma with the old one, they found that it contained much more PF4. Similarly, an injection of PF4 alone into aged animals was as regenerative as young plasma: the treated rodents performed better on a variety of memory and learning tasks. “PF4 makes the immune system look younger by decreasing all the pro-aging factors, leading to a brain with less inflammation, more plasticity, and ultimately more cognition,” Villeda explains. “We’re looking at 22-month-old mice, equivalent to a 70-year-old human, and PF4 gets them back to functioning as if they were in their late 30s, or early 40s.”
A second point in favor of PF4 is scored by Dubal. When the expert demonstrated a decade ago that the Klotho protein improves cognition in young and old animals and makes the brain more resistant to age-related degeneration, she was aware that these effects could be indirect because the molecules of Klotho, injected, they never reached the brain. Dubal’s team discovered that one connection was PF4, released by platelets after injection. PF4 had an important effect on the hippocampus, the brain region responsible for making memories, where it enhanced the formation of new neural connections. She also gave old and young animals a brain boost in behavioral tests, suggesting that “there’s room to go for improved cognitive function in young brains as well.”
And then there is the chapter on physical exercise, and its beneficial effect on humans. Exercise can keep a sharp mind for decades. Again, the scientists have shown, the key is PF4. Walker and his lab discovered that platelets released PF4 into the bloodstream after physical activity. Testing the impact of this factor alone, the Australian team also observed cognitive improvement in the aged animals. “For many people with medical conditions, mobility issues, or advanced age, exercise just isn’t possible, so pharmacological intervention is an important area of research,” concludes Walker. “We can now target platelets to promote neurogenesis, improve cognition and counteract age-related decline.”
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