Nature: Protein TIMP2 in human cord blood is expected to reverse aging
April 24, 2017 Source: Bio Valley
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];In a new study, researchers from the Stanford University School of Medicine found that human cord blood can improve learning and memory in older mice. They identified a protein that is abundantly present in human cord blood but that decreases significantly with age and has the same effect when injected into old mice. These findings may lead to the development of new therapies to treat age-related decline in mental capacity. The relevant research results were published online in the April 19, 2017 issue of Nature, entitled "Human umbilical cord plasma proteins revitalize hippocampal function in aged mice".
Dr. Tony Wyss-Coray, Ph.D., author of the paper and a professor of neurology and neuroscience at Stanford University School of Medicine, said, "What neuroscientists have overlooked and still overlooked is that something in your blood can influence how you think."
In a previously discussed study, the Wyss-Coray laboratory has demonstrated that direct perfusion of plasma from young mice (ie, cells that are free of cells in the blood) is beneficial to older mice.
This new study is the first to demonstrate that human plasma can help improve the memory and learning ability of older mice. Wyss-Coray and the first author of the paper, Dr. Joseph Castellano, said that this suggests that similar effects are also present in the human body. They suggest that from a drug development perspective, it is hoped that a single protein will largely reproduce these benefits.
Age-related changes in the blood
By comparing plasmas from 19 to 24 years old, 61 to 82 years old, and cord blood, these researchers identified age-related changes in a variety of proteins.
These researchers speculate that these changes may affect the hippocampus in the brain. For mice and humans, the hippocampus plays a crucial role in transforming experiences into long-term memory. In particular, the hippocampus is essential to help you remember spatial information and event information that you have personally experienced.
Wyss-Coray said that the hippocampus is particularly vulnerable to normal aging, given largely unknown reasons. He said, "As the age increases, the hippocampus degenerates, loses nerve cells and shrinks." The ability to learn and remember is difficult to maintain. Degeneration of the hippocampus is also an early manifestation of Alzheimer's disease.
To distinguish the effects of blood from older people, blood from young people, and blood on human hippocampus, these researchers used immunodeficient laboratory mice to receive human plasma injections multiple times without going through negative immune response. Experiments prior to receiving human plasma injections have shown that the hippocampal activity, integrity, and regenerative capacity of these mice declines in old age, as they do with normal immune function - indeed, the decline is somewhat faster.
Older immunodeficient mice perform worse than younger mice in memory and learning tests. One of the tests, the Barnes maze, was tested using a rotatable circular platform. The platform has a diameter of 122 cm and a height of 40 cm. This platform is bright and open relative to the surrounding environment. The perimeter of the platform is also filled with round holes. A round hole is attached to a tube that is connected to a dark, narrow box (ie, target box) below it. After training, animals such as mice can learn and remember the position of the target box. Through this tube, frightened mice can find darkness and safety. The other round holes are hollow and are not associated with any objects.
Hippocampus function improvement
When the old mice received human cord blood plasma injections every four days for two weeks, many indicators of hippocampal function improved significantly. On the other hand, plasma from the elderly does not work at all, and plasma in young people induces an intermediate effect. Older mice receiving human plasma injections showed significant improvement in Barnes maze and other tests compared to mice of the same age receiving saline instead of plasma.
A component of human cord blood makes the brains of older mice appear younger. To find out what it is, Wyss-Coray and his colleagues measured plasma protein levels in humans and mice of different age groups in order to find out which proteins are present in both species, and which protein levels are age-related. The increase plays a similar change. One protein particularly attracted their attention: in a laboratory test aimed at finding a substance that increases the activity of nerve cells in the brain, the protein greatly enhances this activity. This protein, known as tissue inhibitor of metalloproteases 2 (TIMP2), belongs to one of the four known families of TMIP proteins.
Injection of TIMP2 into aged mice can largely reproduce the beneficial effects of human cord blood. It even restored the nesting ability of these mice. Nesting with available materials (such as the cotton bolus provided by these researchers) is an instinct for mice, but this instinct is largely lost in old age. However, older mice receiving plasma cord blood injections from humans lacking TIMP2 did not improve their learning and memory. Injecting TIMP2 neutralizing antibodies into young normal mice (usually well in memory) can completely destroy their superior memory.
"The impact of TIMP2 in the brain has been studied in a small amount, but it has not been extensively studied, and the effects on aging have not been studied," Castellano said. In our study, it reproduces the use of human cord blood. Memory and learning influence. It seems to do this by improving hippocampus function." (Bio Valley Bioon.com)
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