Study: protein in human umbilical cord blood rejuvenates old mice

New research from Stanford University shows umbilical cord blood from human newborns, and in particular a single protein contained in it, boosted old mice's brain function and cognitive performance.

The protein, abundant in human cord blood but decreasingly so with advancing age, had the same effect when injected into the animals.

"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 Tony Wyss-Coray, professor of neurology and neurological sciences and senior author of a study published online in Nature.

In an earlier study, Wyss-Coray's lab showed that direct infusion of young mice's plasma, the cell-free portion of blood, benefited old mice, according to a news release from Stanford. The researchers found that those benefits extended beyond biochemistry and physiology to actual performance on tests of memory and learning.

The new study marks the first demonstration that human plasma can aid older mice's memory and learning, which both Wyss-Coray and lead author Joseph Castellano, a former postdoctoral scholar and now an instructor of neurology and neurological sciences, said would seem to increase the likelihood that it could have a similar beneficial effect in people.

While it is also promising from a drug-development standpoint, they suggested, that a single protein appears largely capable of mimicking those benefits, the findings could lead to new treatments for age-associated declines in mental ability.

Comparing blood plasma from 19- to 24-year-olds, 61- to 82-year-olds and umbilical cords, the researchers identified age-associated changes in a number of proteins. These changes, they suspected, might affect a brain structure called the hippocampus, which in both mice and humans is critical for converting experiences into long-term memories. In particular, the hippocampus is essential for helping humans remember spatial information and information about autobiographical events.

For largely unknown reasons, the hippocampus is especially vulnerable to normal aging. "With advancing age, the hippocampus degenerates, loses nerve cells and shrinks," Wyss-Coray said. The capacity to learn and remember falters in lockstep. Hippocampal deterioration is also an early manifestation of Alzheimer's disease.

To distinguish the effects of old, young and "youngest" human blood on hippocampal function, the researchers used immune-deficient laboratory mice that could be given repeated injections of human plasma without experiencing negative immune reactions. Experiments undertaken before injecting human plasma into the mice showed that, like their immune-competent peers, these mice's hippocampal activity, integrity and regenerative capacity dropped off in old age.

When the older mice received human umbilical-cord blood plasma every fourth day for two weeks, many measures of hippocampal function improved notably. Plasma from older people, on the other hand, didn't help at all, while young-adult plasma induced an intermediate effect.

To find out what was making old brains act younger, Wyss-Coray and his colleagues gauged plasma-protein levels in humans and mice from different age groups, in search of proteins that the two species share in common and whose levels change similarly with age. One protein in particular grabbed their attention: tissue inhibitor of metalloproteases 2, or TIMP2.

TIMP2 belongs to a well-known family of four TIMPs that regulate the activity of other proteins whose function is to chop up yet other proteins occupying the matrix in which cells are embedded.

Injecting TIMP2 into elderly mice largely duplicated the beneficial effects of umbilical-cord plasma. "TIMP2's effects in the brain have been studied a little, but not much and not in aging," said Castellano. "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." Endit