Researchers at Stanford University School of Medicine may have recently stumbled upon a real-life fountain of youth for the mind. In their study, published in Nature on April 19th, the researchers reported that a protein found in human umbilical cord blood plasma improved memory and learning in older mice.
When they compared blood plasma from people ages 19 to 24, ages 61 to 82, and plasma from umbilical cords, the researchers found that a number of proteins underwent age-associated changes such as age-related elevated antibody levels. They suspected that these changes may affect the hippocampus, a region of the brain associated with spatial navigation and memory, and particularly, the storage of long-term memories. This brain structure undergoes aging, loses nerve cells, and shrinks with time. In addition, it is vulnerable to damage due to Alzheimer’s disease.
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The researchers used immune-deficient laboratory mice to test the differences between older and younger blood. In other words, these mice were repeatedly injected with human blood plasma without interference from their immune systems. Just like normal mice, the hippocampal function and activity of these mice decreased with old age. Moreover, older mice performed worse than younger mice in memory and learning tests, such as the classic Barnes maze test.
When injected with umbilical cord plasma, hippocampal function of the mice improved significantly. However, plasma from older people had little effect, and plasma from young adults caused an intermediate effect on improving hippocampal function. There was something in the umbilical cord plasma that revitalized the hippocampus and improved learning and memory in the mice. To track down what this unknown factor was, the scientists investigated blood plasma protein levels in both humans and mice of different age groups. They honed in on one particular protein, TIMP2 (tissue inhibitor of metalloproteinases 2).
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Pure TIMP2 injections in elderly mice had almost the same beneficial effects of umbilical cord plasma injections. The researchers went on to test how TIMP2 depletion affected mice. Elderly mice injected with plasma lacking TIMP2 showed no improvement in memory or learning. Blocking TIMP2 in young mice by injecting TIMP2-neutralizing antibodies also impaired memory.
These findings have significant implications for the field of regenerative medicine, including possible drug treatments for disease or age-associated declines in mental ability related to hippocampal function. According to the study’s senior author, Tony Wyss-Coray, Ph.D., despite these compelling results, TIMP2 isn’t the whole story, as there may be several individual factors in the blood that improve brain function. However, as Wyss-Coray expressed to Bruce Goldman, science writer for Stanford University School of Medicine, “it’s remarkable that something in your blood can influence the way you think.”
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