Step forward platelet factor 4 (PF4): this substance in the blood has been linked to the mental boost we get from exercise, the benefits of blood transfusions, and a protein associated with longevity, in three separate studies.

All three processes promote cognitive enhancement, meaning PF4 is something of a superpowered blood factor. The research was carried out by two teams from the University of California San Francisco (UCSF) in the US and the University of Queensland in Australia.

Platelets are cell fragments that play a critical role in the clotting process. Aside from serving as physical plugs that staunch bleeding, these small, non-nucleated chunks of bone marrow cell contain granules that release chemicals to promote aggregation.

As one of these factors, the protein PF4 contributes to the immune system’s response to injury and infection.

Now it appears to play a role in anti-aging mechanisms as well, under the direction of an enzyme expressed in quantities in the brain, liver, and kidneys known as klotho.

“Young blood, klotho, and exercise can somehow tell your brain, ‘hey, improve your function’,” says UCSF anatomist Saul Villeda.

“With PF4, we’re starting to understand the vocabulary behind this rejuvenation.”

In the case of the young blood study, older mice were injected with PF4, which was shown to reduce inflammation in the brain and improve the memory of the animals. Essentially, it reversed some of the deterioration that comes with getting older.

The study builds on previous research into what’s known as parabiosis, where blood from younger humans or other animals can have a rejuvenating effect. One of the characteristics that younger blood tends to have is more PF4.

In the second of the three studies, again using mice, the scientists were able to link PF4 to the membrane protein klotho. Klotho had previously been shown to boost cognitive powers, and it turns out that PF4 helps in transferring that boost to the right brain regions.

Both young mice and old mice improved in behavioral tests after an injection of klotho, which subsequently releases PF4. This enhanced the formation of new connections in the hippocampus, which is where the brain makes memories.

Last but by no means least, the third study found exercise releases more PF4 into the blood of mice. PF4 was observed playing a role in the creation of new brain cells, and also improved memory functions in older mice.

We already know that exercise can help to keep the mind sharp, and it seems PF4 plays a role in that. In the future, therapies could be developed that deliver the benefits of exercise for those who are unable to be active in a normal way.

While these studies were all carried out on mice, it’s thought these findings will mostly likely apply to the human body too, suggesting multiple ways PF4 “messengers of brain health” might help in future treatments.

“When we realized we had independently and serendipitously found the same thing, our jaws dropped,” says UCSF neurologist Dena Dubal.

“The fact that three separate interventions converged on platelet factors truly highlights the validity and reproducibility of this biology.”

The research has been published in Nature, Nature Aging, and Nature Communications.