A protein found in the plasma of human umbilical cord blood perked up the memories of elderly mice, researchers reported Wednesday in Nature.
Researchers at Stanford had first noted that injecting middle-aged mice with plasma from human cord blood could boost activity in their hippocampi, an area of the brain critical for creating and banking memories. The mice also got better at memory tests. After some analysis, the researchers focused in on one plasma protein called TIMP2. With injections of just that protein, the senior rodents again improved on memory and learning tests (though not quite to the extent that mice given whole plasma did). Still, they became faster at navigating a maze and restored nesting skills they lost with age, and they could better remember a chamber where their feet get zapped with a slight electrical shock.
TIMP2 is an intriguing find in the pursuit of anti-aging therapies; TIMP2 levels in the blood of mice and men start high in life but then wane in later years. And the researcher found that blocking TIMP2 in young mice seemed to prematurely age their memories.
But the findings are still only in mice—they may mean nothing for humans, and TIMP2 treatments may be unsafe in older adults. And debate still swirls around how to pursue anti-aging research and what this new finding might mean. For instance, as Irina Conboy, a researcher who studies aging at the University of California, Berkeley noted to NPR, TIMP2 levels are elevated in people with Alzheimer’s disease. And it’s still unclear how TIMP2 might tinker with our brains.
Age-old pursuit
The new finding is just the latest in decades of work trying to find a remedy for the assault of time on the body. Long ago, researchers stitched mice together, connecting their circulatory systems, to show that young blood pumped into old mice could rejuvenate them. And more recent work had tracked the benefits down to mysterious contents of plasma.
Back in 2014, researchers reported data suggesting that another plasma component, called GDF11, seemed to spur the growth of blood vessels and neural stem cells.
The new findings don’t negate or conflict with the findings of GDF11, the authors of the new study as well as those of the GDF11 work said. Harvard neuroscientist Lee Rubin, a coauthor of some of the GDF11 work, told Science that the new data suggests that “it isn’t just one thing. A lot of individual factors in blood can improve function.” (Rubin is an advisor to a company called Alkahest, which is studying using plasma to treat Alzheimer’s and was cofounded by one of the authors of the new study, Stanford’s Tony Wyss-Coray.)Stanford neuroscientist Joseph Castellano, lead author of the new study, told NPR, “The only thing, of course, is that it's a mouse experiment, and mouse experiments often don't actually translate faithfully into the human setting.”
And other researchers, such as Berkeley’s Conboy, think that the Castellano team is looking at things the wrong way entirely—it may not be that old blood lacks good components but that it may contain accumulated bad stuff. In her work, she hasn’t seen any positive brain effects of swapping old blood for new blood.
"We have hundreds of proteins that change with age," she said. If there are any therapies in the (distant) future that can turn back the clock, they will likely involve fiddling with several of them.
Nature, 2017. DOI: 10.1038/nature22067 (About DOIs).
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