In an earlier study widely discussed by the scientific community, the authors demonstrated that the administration of human plasma (a liquid blood component) can have a positive effect on the memory of mice and their ability to learn. Based on this, they hypothesized that a similar effect could be observed in humans. This fact is also interesting from the point of view of developing “rejuvenating” drugs, because, according to the scientists’ assumption, the observed effects are predominantly due to a single protein. In their new study, they compared the protein composition of the plasma of two groups of people aged 19-24 and 61-82 years, as well as cord blood, and identified age-associated changes in the concentration levels of a number of proteins. The authors hypothesize that these changes may affect the hippocampus, a region of the brain responsible for memory. In particular, the hippocampus is important for remembering spatial information (such as the ability to find a car parked hours ago in a multi-level parking lot) as well as information about autobiographical events (such as what you had for breakfast). For little-understood reasons, the hippocampus is particularly susceptible to the ravages of normal aging processes, which manifests itself in degeneration, nerve cell death, and size reduction. In parallel to this, memory and learning abilities decline. Hippocampal degeneration is also an early manifestation of Alzheimer’s disease. To identify the effects of old, young and “youngest” human blood on hippocampal function, the researchers used immunodeficient mice, which can be repeatedly injected with human plasma without the risk of immunologic rejection reactions. Preliminary experiments showed that the age-related decline in hippocampal activity, integrity and regenerative capacity was slightly faster in animals of this line than in normal animals. Older immunodeficient mice performed more poorly on tests of memory and learning ability than younger animals. In such a test, known as the Barnes maze, mice are placed on a table about 60 centimeters in diameter and 40 centimeters high. The bright lights and large open space induce a sense of danger in the mice. There are many holes in the table, one of which has a tube attached to the bottom where a frightened mouse can find darkness and safety. Through the other holes the animal falls to the floor, a fall from such a height does not hurt it, but it causes unpleasant memories. The location of the pipe attachment can be changed, as can the location of the visual clues leading the animal to the escape hole. Injection of old mice with human umbilical cord blood every other day for two weeks significantly improved many parameters of hippocampal functioning. At the same time, plasma from old people had no effect, and plasma from young people induced intermediate changes. In search of the protein responsible for this effect, the authors analyzed protein levels in the plasma of people of different age groups. Their attention was drawn to tissue inhibitor of metalloproteinases-2 (TIMP2), a protein belonging to a well-known group of 4 tissue inhibitors of metalloproteinases that regulate the activity of proteins whose function is to fragment other proteins in the surrounding cell matrix. The administration of TIMP2 itself to old mice generally reproduced the beneficial effects of cord blood plasma. It even restored the animals’ ability to nest: an instinct normally lost in old age, which involves using available materials, such as cotton balls provided by the researchers, to create nests where the animals like to sleep. At the same time, injecting old mice with TIMP2-depleted cord blood plasma had no effect on memory or learning ability. And the introduction of healthy young animals neutralizing TIMP2 antibodies worsened their results when performing memory tests. The article by Joseph M. Castellano et al. Human umbilical cord plasma proteins revitalize hippocampal function in aged mice is published in Nature. Evgenia Ryabtseva Portal «Eternal Youth» http://vechnayamolodost.ru on materials of Stanford University School of Medicine: Study shows protein in human umbilical cord blood rejuvenates old mice’s impaired learning, memory.