A hormone released by bones seems to reverse age-related memory loss. The hormone can be boosted by exercise, suggesting that lifting weights might protect the brain from the ravages of old age.
Eric Kandel of Columbia University in New York and colleagues were interested in understanding the mechanisms behind normal age-related memory loss.
To investigate, they measured mRNA levels associated with the expression of 23,000 genes in human brain tissue. Genes use mRNA to tell cells to make products such as proteins – mRNA levels therefore reflect how active a gene was before death.
The team focused their analysis on the dentate gyrus, a brain region particularly affected by memory loss as we grow older.
The brain tissue came from eight healthy people aged between 33 and 88. Across these people, one gene — called RbAp48 — became steadily less active with age. This gene is known to be involved in the process by which we turn short-term memories into long-term memories.
Health bones, healthy brain
Kandel’s team went on to show that a relationship exists between RbAp48 and osteocalcin, a hormone secreted by bone.
Osteocalcin has many functions, one of which seems to be involved in cognition – mice who carry a mutation that makes them deficient in the hormone have memory deficits. Replacing this hormone improves their memory.
Osteocalcin’s effects, however, appear to be dependent on the expression of RbAp48 in the dentate gyrus. When Kandel’s team silenced the gene in mice, they had memory deficits in spite of osteocalcin’s presence. Kandel’s team also discovered that mice deficient in osteocalcin have lower amounts of RbAp48 and that injections of the hormone increased the amount of the RbAp48 protein in the dentate gyrus.
Natural decline
The upshot of the research is that osteocalcin, produced by bones, and mediated by RbAp48, appears vital to a healthy memory. This is supported by the fact that age-related osteoporosis in which bones lose their strength and produce less osteocalcin — has been linked to memory loss.
We naturally produce less osteocalcin throughout our lives as our bone mass declines. However, exercise may be able to stop this, says Kandel, who presented his team’s findings at the Society for Neuroscience meeting in Washington DC this month. Previous research has shown that osteocalcin levels increase markedly during endurance exercise in mice and humans. “You need to have healthy bone mass, for health longevity. That’s extremely important,” says Kandel.
“Osteocalcin is necessary and sufficient to improve memory in older mice,”says Gérard Karsenty at Columbia University. “This obviously has great importance in view of the progressive ageing of the general population and therefore the increase in incidence of age-related memory loss in humans.”