Human umbilical blood makes old mice build nests again

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Scientists have reversed memory and learning problems in aged mice with infusions of a protein found in human umbilical cord blood. For example, scientists have shown that young blood can restore cell activity in the muscles and livers of aging mice. This discovery could lead to the development of new therapies to target brain degeneration associated with ageing. Afterwards, the researchers compared those mice with those in three other groups: those that got blood plasma from young adults, those that got plasma from older people, and those in a control group that only got saline. The lesson from Alzheimer's research on mice is that nearly everything works in the animals, and so far nothing works in humans, said Rob Howard, professor of old age psychiatry at University College London.

Similarly, mice treated with human umbilical cord blood performed better on a second memory test. The lead author of the study was Joseph Castellano, Ph.D., an instructor of neurology and neurological sciences.

It turned out that they did - at least when the plasma came from umbilical cords.

That experience occurs more frequently as we get older, because the functions of the part of the brain that encodes spatial and episodic memories - the hippocampus - decline with age.

For largely unknown reasons, the hippocampus is especially vulnerable to normal aging, said Wyss-Coray.

In the meantime, a clinical trial created to test whether young human plasma can slow the cognitive decline of people with Alzheimer's disease is under way. (Its full name is tissue metallopeptidase inhibitor 2.) Old mice injected with mouse TIMP2 scored nearly as well on memory tests as those given cord plasma, although they still didn't match the cognitive skills of young mice, Wyss-Coray says. A Nature Communications study published in November also suggested transferring blood between young and old mice provided little benefit, and suggested "the inhibitory effects of old blood are more pronounced than the benefits of young".

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

Before being injected with umbilical cord blood, Castellano says, "their performance wasn't very impressive".

It was the beginning of a peculiar and ambitious scientific endeavor to understand how certain materials from young bodies, when transplanted into older ones, can sometimes improve or rejuvenate them.

First off, he says, there's no evidence that elderly humans would experience the same effects as the mice did in this study. The mice aged between 12 and 14 months old that is equivalent to being in the late 50s and 60s. And when they injected plasma containing TIMP2 into elderly mice, they again observed improvement in memory and learning tasks.

Something in umbilical cord blood was making old brains act younger. This suggests that human plasma gradually loses its rejuvenating potential with age. The mice with the younger injection showed more activity in the hippocampus, and much improved maze performance.

And other researchers are more skeptical - Rob Howard from the University College London, who also wasn't involved in this paper, told The Guardian that the lesson from Alzheimer's research so far is that "almost everything works in the animals, and so far nothing works in humans". According to scientists, it appears the same is true for older mice. The other holes offer only a drop to the floor from a height that would not physically harm a mouse but is enough deter one.

Valdez said that the therapeutic potential could extend beyond TIMP2-to endogenous factors that cause levels of the protein to decrease with aging.

"So, we had a hint early on that one of these donor groups, specifically the [umbilical] cord plasma, might be having an effect on the brain itself", he says.

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