As we age, memory function tends to suffer. Understanding and preventing this creeping deficit is a priority for many scientists. Now, a recently published study brings us one step closer.
With age comes a decline in certain aspects of our cognitive ability. It may not be the case for everyone, and not everyone is affected in the same way, but memory generally worsens.
As our average lifespan increases, so too does interest in the negative impacts that aging has on the mind — and how to prevent or slow them, of course.
To date, researchers have identified hundreds of genes that are involved in the aging process. For instance, in 1988, scientists discovered that a certain gene mutation in Caenorhabditis elegans (a type of worm) could extend maximum lifespan by up to 110 percent.
Since then, more than 800 individual genes have been identified that influence the lifespan of C. elegans, and many more in other species. Although the genes involved in aging are slowly being unfurled, understanding what they do and how to influence them is another challenge entirely.
Recently, Philip Landfield, John Gant, Eric Blalock, and colleagues from the University of Kentucky in Lexington carried out a multipronged study. They wanted to understand the role of a specific protein in age-related memory decline in rats, and how it influences age-related gene changes.
The protein, called FK506-Binding Protein 12.6/1b (FKBP1b), regulates calcium homeostasis in the neurons of the hippocampus, which is a region of the brain involved in spatial memory and converting short-term memories into long-term ones.
When researchers look for changes in the way that the aging brain works, they consistently find alterations in the way that calcium carries out physiological roles.
Earlier work by the same team found that disrupting FKBP1b interfered with hippocampal calcium usage. The study authors also found that expression of the FKBP1b gene was down-regulated in the hippocampus of aging rats and humans with early stage Alzheimer’s disease.
For their latest study, they wanted to examine how FKBP1b treatment in aging rats might influence memory performance and age-related genetic changes.
They injected rats with viral vectors that expressed FKBP1b, causing a rise in overall expression of the protein. The injections were given either at 13 months old, before cognitive decline begins (referred to as long-term), or at 19 months old, once decline had begun (called short-term).
Their findings are published this week in The Journal of Neuroscience.
Both long- and short-term treatment improved the performance of aging rats in a water maze task: FKBP1b was able to prevent cognitive decline in long-term rats and reverse it in short-term rats.
The treated rats completed memory tasks better than untreated rats of the same age, and their scores were more in line with young, untreated rats.
Next, the researchers carried out transcriptional profiling. They identified 2,342 genes expressed differently in young and old animals. Treatment with FKBP1b restored activity in 876 of these age-affected genes. In fact, levels were similar to those of untreated young rats.
The genes that showed changes might “represent a new genomic network” involved in regulating the structure and function of the hippocampus that falls into disrepair with age. The authors conclude:
“[T]his genomic evidence adds strong new support for the hypothesis that FKBP1b is a linchpin of neuronal homeostasis that functions at multiple levels, including regulation of [calcium], maintenance of structural integrity, and preservation of cognitive function.”
These recent findings provide further evidence that FKBP1b plays a significant role in cognitive aging and, in particular, memory decline. Because calcium dysfunction appears to play a role in Alzheimer’s disease, the results may also be useful for researchers in that field.