A recent study from Stanford University School of Medicine demonstrates the partial restoration of brain function in old mice with infusions of cerebrospinal fluid (CSF) from younger mice. CSF surrounds the brain and spinal cord and is critical in maintaining a healthy brain by transporting nutrients, cellular waste, and hormones in to and out of the nervous system. Maintaining an organism’s supportive fluid systems, such as cerebrospinal fluid, is gaining greater attention as a means of restoring a more youthful phenotype in research animal models. Specifically, the transfusion of blood and plasma from younger or healthier organisms to their older, more decrepit counterparts has been shown to impart restorative properties in laboratory animals. This has led to similar approaches utilizing other supportive matrices such as the microbiota of the gut and, in this study, CSF.

Older mice treated with the CSF of young mice showed improved memory on a standard laboratory test to assess memory formation and consolidation—a cognitive function known to deteriorate with age. The researchers conducting this study believe this might be due to the observed proliferation of cells within the hippocampus, a region of the brain highly involved in memory function. Further interrogation of this region revealed an increase in serum response factor (SRF), a protein that decreases with age. SRF belongs to a family known as transcription factors, which have the ability to regulate gene expression. Further tests revealed SRF to mediate the increase in hippocampal cells, specifically oligodendrocytes, observed in mice treated with the CSF of young mice.

In an attempt to further characterize the mechanisms responsible for the improvements in memory, a subsequent profiling determined a specific protein, Fgf17, to be an activator of SRF. Fgf17 is one of the proteins known as fibroblast growth factors, of which a number have been implicated in improving and/or maintaining healthspan. Further experiments were designed to assess Fgf17’s relevance in supporting the enhanced memory seen in old mice transfused with the CSF of young mice.

Experiments involving Fgf17 carried out in cultured cells produced results similar to those in mouse model experiments. Fgf17-treated cells showed both an increase in SRF activity and an increased proliferation in oligodendrocytes—the same cells found to be increased in the memory region of mouse brains treated with young CSF. In addition to the findings of the cultured cell experiments, mice treated with an antibody that inhibited the action of Fgf17 performed poorly on a series of standard memory tests.

Aging is characterized by an array of dysfunctions in multiple organ systems, e.g., cardiovascular disease, diabetes, arthritis, and kidney disease; however, in humans perhaps the most tragic are dysfunctions of the brain. Severe memory loss associated with neurodegenerative diseases such as dementia and Alzheimer’s disease places an enormous emotional and economic burden on both the families and the communities that support these individuals, and with a rapidly growing geriatric population and no known therapies, the future looks very bleak. According to the CDC, an estimated 5.8 million people over age 65 suffer from Alzheimer’s disease, a population predicted to triple by 2060. However, studies such as these may lead to adequate therapeutics desperately needed to address this impending plight.