Researchers here argue that failing calcium regulation provides a meaningful contribution to neurodegeneration, and demonstrate improvement in old rats via altered levels of a protein involved in calcium metabolism. As is the case for most research, this identifies only one step of cause and consequence in longer chain of events. We should expect, given the necessary time and resources, for researchers to be able to trace back age-related changes to fundamental forms of cell and tissue damage that occur as a side-effect of the normal operation of cellular metabolism. That is a long road, however, and given that we already have a catalog of those fundamental forms of damage, it would be faster to start by repairing them to see what happens. That approach is still a minority concern in the research community, sadly.
Building on scientific evidence implicating disturbed calcium regulation in brain aging accumulated through the past 30 years, a research team has found a connection between unhealthy brain aging and a protein responsible for regulating calcium at the molecular level, called FKBP1b. Excess calcium in brain cells appears responsible for important aspects of unhealthy brain aging, and may also increase susceptibility to diseases such as Alzheimer's, ALS, Parkinson's and vascular dementia. Until now, the precise molecular cause of the disturbed calcium regulation in brain aging has remained unknown to scientists. After learning about the FKBP1b protein's recently uncovered role in the heart, researchers wondered whether FKBP1b in the hippocampus region declines with brain aging. They then found evidence of reduced FKBP1b gene expression with aging in the hippocampus. This discovery prompted the researchers to test whether boosting FKBP1b in the hippocampus region could reverse or prevent brain aging linked to memory loss.
The team used an advanced gene therapy approach to inject harmless virus particles, which created additional copies of the FKBP1b protein, into the hippocampus of aging rats. The memory abilities of three groups of rats were tested two months after the injections. One group of young rats received a control injection, one group of aged rats received a control injection and one aged group received an injection of the FKBP1b-producing virus particles. The aged group with raised levels of FKBP1b showed restored calcium regulation and dramatically improved cognitive function, allowing them to perform the memory task as well as or better than the young rats. In addition, the researchers have repeated and extended the results in a subsequent study being prepared for publication.
The research provides evidence the manifestations of brain aging can be reversed, and cognition and memory function restored, by altering levels of FKBP1b. This finding is also significant for Alzheimer's patients as the researchers found a decline in the FKBP1b protein in the hippocampus of people who had early-stage Alzheimer's. The research has implications for preventing brain aging associated with the progression of Alzheimer's, and opens the door for pharmaceutical development aimed at sustaining levels of FKBP1b and keeping calcium in check.