Discovery Lecturer Kandel tackles age-related memory loss

Eric Kandel, M.D., poses for a photo with Elaine Sanders-Bush, Ph.D., following his Flexner Discovery Lecture last week. (photo by Susan Urmy)

Eric Kandel, M.D., who was awarded the Nobel Prize in 2000 for discovering molecular mechanisms of memory storage, told the crowd at last week’s Flexner Discovery Lecture that he has recently become interested in memory in the aging brain.

“We’ve been studying age-related memory loss, and not a moment too soon,” quipped the 87-year-old Kandel, University Professor and Fred Kavli Professor in the Department of Neuroscience at Columbia University.

Kandel summarized decades of research into the molecular underpinnings of memory. His team used the marine snail Aplysia to study a simple reflex behavior — the withdrawal of the gill when the animal is touched or shocked, like pulling the hand away from a hot object.

The simple nervous system and large nerve cells of Aplysia made it possible for Kandel and his colleagues to work out the neural circuitry for the reflex and to determine the molecular mechanisms that distinguish short-term from long-term memory.

“There are many people in the field…who think that the Aplysia rather than the investigator should have won the Nobel Prize,” Kandel said.

In more recent work, Kandel and his colleagues have turned their attention to age-related memory loss. The researchers wondered, Kandel said, if memory loss during normal aging is a distinct process or an early phase of Alzheimer’s disease.

They determined that mice, which do not experience spontaneous Alzheimer’s disease, also experience age-related memory loss, suggesting that the two processes are distinct, he said. Other studies showed that brain regions involved in age-related memory loss and Alzheimer’s disease are different.

In studies of post-mortem brain samples from people ages 38-90 who did not have Alzheimer’s disease, the researchers discovered that the expression of the gene RbAp48 decreased with age in the dentate gyrus — the brain region implicated in age-related memory loss. They went on to demonstrate that RbAp48 is part of the molecular machinery of long-term memory.

Further studies implicated osteocalcin, a hormonal factor released by bone, as a “general memory enhancer.” Osteocalcin levels decrease over the lifespan, but exercise increases osteocalcin levels, Kandel noted.

Kandel offered a prescription for age-related memory loss: get regular exercise to increase osteocalcin, and continue to work and to learn.

“Don’t retire early,” he said with a grin.

Kandel’s lecture was the Elaine Sanders-Bush Lecture sponsored by the Department of Pharmacology. For a complete schedule of the Flexner Discovery Lecture series and archived video of previous lectures, go to mc.vanderbilt.edu/discoveryseries.