With age, our memory and cognition tend to decline. But could osteocalcin soon be used to reverse these effects?
Conducted in mice, the new research was carried out by scientists led by Dr. Gerard Karsenty, who is the Paul A. Marks Professor and Chair of the Department of Genetics & Development at the Columbia University Medical Center in New York.
Previous research co-authored by Dr. Karsenty has shown that osteocalcin – which is a hormone produced by osteoblasts, or bone cells – fulfills a range of metabolic functions in the human body, and that it influences spatial learning, memory, and the birth of new neurons in mice.
In addition, another study led by Dr. Karsenty showed that osteocalcin jabs can restore muscle function in aging mice, bringing it to the same levels as those of their young counterparts.
He explains how this prompted the new research: “We also observed that the hormone declines precipitously in humans during early adulthood. That raised an important question: Could memory loss be reversed by restoring this hormone back to youthful levels?”
Osteocalcin reverses memory decline
To answer this question, Dr. Karsenty and colleagues conducted a series of experiments in aging mice. In one experiment, 16-month-old mice received continuous infusions of osteocalcin in their blood over a period of 2 months.
The researchers also took blood plasma from young mice that did not have enough of the hormone, added osteocalcin, and injected it into aging mice.
They also reduced the osteocalcin levels of normal young mice by adding anti-osteocalcin antibodies to their blood plasma.
After subjecting the rodents to memory tests, the researchers found that blood infusions of the hormone improved the mice’s memory. In fact, osteocalcin seemed to boost the mice’s memory to levels equivalent to those of young mice.
Furthermore, osteocalcin-enhanced plasma transfusion from osteocalcin-deficient mice to old mice also significantly boosted the latter’s performance in memory tests.
By contrast, the mice that received a plasma transfusion from osteocalcin-deficient mice did not perform any better in memory tests, and young mice whose osteocalcin levels were artificially decreased fared worse than their normal counterparts.
The scientists also note that the hormone seemed to “decrease anxiety-like behavior” in the aging mice. Overall, the results of the experiments suggested a resounding “yes” in answer to the initial question that spurred the scientists’ research.
“Could memory loss be reversed by restoring this hormone back to youthful levels? The answer, at least in mice, is yes, suggesting that we’ve opened a new avenue of research into the regulation of behavior by peripheral hormones.”
Dr. Gerard Karsenty
Encouragingly, the rodents did not present with any toxic side effects from receiving osteocalcin. “It’s a natural part of our body, so it should be safe,” says Dr. Karsenty. “But of course, we need to [conduct] more research to translate our findings into clinical use for humans.”
The team also wondered whether they could identify a neuronal receptor for osteocalcin. To do so, they genetically designed a mouse model wherein the rodents had the Gpr158 receptor “switched off.” Gpr158 receptors are located in the hippocampus, which is the brain area responsible for creating and storing new memories.
Then, the researchers administered these rodents osteocalcin infusions. Unlike active Gpr158 mice, the researchers did not see any memory improvements in the mice that had these receptors deactivated.
“These results indicate that exogenous [osteocalcin] can improve hippocampal-dependent memory in mice and identify molecular tools to harness this pathway for therapeutic purposes,” the authors conclude.