Umbilical cord blood could hold the key to restoring the learning and memory ability that declines with age, find researchers at the Stanford University School of Medicine in California. The researchers suggested that it was likely that similar beneficial effects would be seen in humans. Specifically, the team pinpointed a protein in the umbilical cord plasma – which is abundant in human umbilical cord blood but decreases with age – that was capable of mimicking the rejuvenating effect on old mice’s brain function without the need to inject the rest of the plasma. This single protein could prove useful from a drug development perspective. “Neuroscientists have ignored it and are still ignoring it, but to me it’s remarkable that something in your blood can influence the way you think,” said the study’s senior author, Tony Wyss-Coray, a professor of neurology and neurological sciences as well as a senior research career scientist at the Veterans Affairs Palo Alto Health Care System in California. The lead author of the study was Joseph Castellano, an instructor of neurology and neurological sciences. Wyss-Coray, Castellano, and colleagues compared umbilical cords, blood plasma from 19- to 24-year olds, and blood plasma from 61- to 82-year olds in order to identify changes that are associated with age in a number of proteins. The researchers suspected that these age-associated changes might have an effect on the hippocampus, the brain structure critical for “converting experiences into long-term memories” in both humans and mice. The hippocampus is particularly vulnerable to the normal aging process, although the exact mechanisms behind its vulnerability are largely unknown. “With advancing age, the hippocampus degenerates, loses nerve cells, and shrinks,” explains Wyss-Coray. The ability to remember and learn are negatively impacted as a result. The deterioration of the hippocampus is also connected with an early appearance of Alzheimer’s disease. The researchers tested the effect of old and young human blood, as well as the most youthful human blood of all – umbilical cord blood – on the hippocampal function of mice. Older mice received injections of plasma from older adults, younger adults, and human umbilical cord every fourth day for 2 weeks. Human umbilical cord plasma significantly improved hippocampal function. In fact, the performance of the mice from the umbilical cord group was stellar compared with that of mice of the same age that received a sham injection of saline as opposed to plasma, according to the researchers. The researchers aimed to isolate the factor in umbilical cord blood that was making the old brains act younger. To do this, the team evaluated plasma-protein levels in humans and mice from different age groups. They looked for proteins that human and mice have in common, and whose levels fluctuate similarly as they age. One protein, called tissue inhibitor of metalloproteases 2 (TIMP2), was identified that enhanced nerve-cell activity in the brain in a laboratory experiment. When TIMP2 was injected into older mice by itself, the protein replicated the positive effects of the umbilical cord plasma. Furthermore, the nesting instinct of the mice, usually lost in old age, was restored. Joseph Castellano said that “TIMP2’s effects in the brain have been studied a little, but not much and not in aging. In our study, it mimicked the memory and learning effects we were getting with cord plasma. And it appeared to do that by improving hippocampal function.”