In this study, the research team looked at the effects of the liquid part of human blood, called plasma, on mouse brains. This discovery could lead to the development of new therapies to target brain degeneration associated with ageing.
Valdez said that the therapeutic potential could extend beyond TIMP2-to endogenous factors that cause levels of the protein to decrease with aging.
In this study, the scientists injected old mice with blood plasma - the fluid that carries blood cells - taken from human umbilical cords. Mice that received cord plasma fared better than those who received young adult plasma.
Moreover, old mice that were treated with cord plasma that had been stripped of TIMP2 showed no cognitive improvement, confirming that the protein is responsible for the strong anti-ageing effect.
A protein in umbilical cord blood boosted memory in old mice. The lead author of the study was Joseph Castellano, Ph.D., an instructor of neurology and neurological sciences.
When they injected young mice with anti-TIMP2 antibodies to neutralize the endogenous protein, the animals' performance on a spatial memory task deteriorated.
Aging changes the way the brain works and the hippocampus, a region of the brain that helps with learning and memory, is often left impaired. The hippocampus is particularly vulnerable to the normal aging process, although the exact mechanisms behind its vulnerability are largely unknown. Wyss-Coray wondered if TIMP2 suppresses signals from senescent cells, including microglia and astrocytes, which help drive the aging process. The capacity to learn and remember falters in lockstep. The deterioration of the hippocampus is also connected with an early appearance of Alzheimer's disease. Previously Wyss-Coray's group had shown that injecting old mice with blood from young mice improved their cognition, he says.
But, scientists caution, it does not mean people should start ordering umbilical cord blood online. Numerous earlier studies relied on a process called parabiosis, in which pairs of young and old mice had their veins and blood supplies connected.
Plasma from older adults had no effect on measures of hippocampal function, and plasma from younger adults slightly improved hippocampal function. The team then ran the animals through the memory experiments. For example, older mice stop building nests, and they tend to become forgetful, taking a long time to remember how to escape from a maze. They subsequently dissected the mouse brains and found that a subset of genes linked to memory (making new memories) had been turned on in some of the mice. There's a lot of it in cord blood but not so much in older blood. The mice were split into three groups, each receiving plasma from different sources.
Pinning down how TIMP2 influences the brain is the next priority, say Wyss-Coray and Castellano. Injecting TIMP2 alone into aged mice revitalized their hippocampi, improving neural plasticity and performance on several memory tests. Furthermore, the nesting instinct of the mice, usually lost in old age, was restored. "Because it has broad effects, we may actually have a more powerful factor". Immunodepleting cord plasma of TIMP2 also neutralized its effects on LTP and memory in wild-type mice. Electrophysiology of hippocampal slices from the infused mice revealed stronger long-term potentiation (LTP), a sign of improved neural plasticity, only in mice that had received cord plasma.