Older mice’s brains are regenerated by a protein found in the young’s blood
Mouse hippocampus. Aging-related changes in this region of the brain are partly reversed in mice receiving doses of a molecule called platelet factor 4 (PF4).Credit: The Mark and Mary Stephens Institute for Neuroimaging and Informatics/Science Image Library
A protein involved in wound healing could improve learning and memory in aged mice1.
Platelet factor 4 (PF4) has long been known for its role in promoting blood clotting and bridging broken blood vessels. Now, researchers are wondering if this signaling molecule could be used to treat age-related cognitive disorders such as Alzheimer’s disease.
“The therapeutic possibilities are very exciting,” says geneticist and anti-aging scientist David Sinclair of Harvard University in Boston, Massachusetts, who was not involved in the research. The study was published August 16 in the nature.
Young blood, old minds
About a decade ago, scientists discovered that blood from young mice could restore youthful characteristics, including learning abilities, in older mice.2And3. The idea captivated Saul Villeda, a neuroscientist at the University of California, San Francisco and co-author of the new study. He and his colleagues have been trying since then to identify the components of the blood that cause this regeneration.
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Several lines of evidence have suggested that PF4 may be one of these components, including the fact that young mice had higher levels of this molecule in their blood than older mice. Vileda and colleagues attempted to inject PF4 into aged mice without including other blood components. The researchers found that the proportions of different types of immune cells turned out to be more similar to what we normally see in younger mice. Some immune cells have also reverted to a more youthful pattern of gene expression.
Although PF4 was unable to cross the blood-brain barrier, its effect on the immune system also led to changes in the brain, possibly through indirect mechanisms. Old mice that received doses of PF4 showed a reduction in destructive inflammation in the hippocampus – a part of the brain that is particularly vulnerable to the effects of aging. They also showed increases in levels of molecules that promote synaptic plasticity (the ability to alter the strength of connections between neurons).
Old mice injected with PF4 also performed better than elderly control mice on cognitive tests, such as remembering where to find a submerged platform on which they could rest when forced to swim through a maze.
plus platelets
Prior to this study, platelet biologist Robert Campbell of the University of Utah in Salt Lake City said, “Prior to this study, no one, as far as I know, had really shown that platelets could play a role in cognition.” “I was really excited about it.”
Two other publications released today also suggest that PF4 has a role in regulating the hallmarks of aging. Dina Dubal and her colleagues at the University of California, San Francisco, found that PF4 enhances synaptic plasticity4and Tara Walker and colleagues at the University of Queensland in Brisbane, Australia, have shown that PF4 is involved in the formation of new neurons.5.
The first hint that the body’s “biological age” can be reversed
PF4 is one of the few aging-related molecules identified by Villeda et al. in recent years. Some are involved in cognition, others are associated with aspects of aging such as muscle loss, and still others have multiple functions.
Biotech companies, including Elevian and Alkahest, are trying to turn these discoveries into treatments that promote regeneration and healthy aging. Treatments will likely need to take a range of aging-related factors into account, says Vileda, and different combinations of treatments may be appropriate for different people.
If a decline in PF4 levels is shown to precede Alzheimer’s disease, this molecule could be used as a biomarker to identify people who might benefit from other therapies, says physiologist Cheryl Conover at the Mayo Clinic in Rochester, Minnesota. Some of the current treatments for Alzheimer’s disease work best if they are used during the early stages of the disease, so it’s helpful to find a way to identify those at risk before they develop symptoms.
