Protein May Reverse Age-Related Memory Loss

Researchers looked at the brains of young and old mice. Some had access to a running wheel in their cage, while others did not. The team found changes in the part of the brain called the hippocampus. This area is important for learning and memory.

Older mice that were physically active had more brain cells called neurons in the hippocampus and made fewer errors on learning and memory tasks.

The team then injected older, less active mice with blood plasma from other mice. Older mice given plasma from active mice showed increases in neurons, learning, and memory performance similar to active mice.

Researchers linked these brain benefits to a protein called GPLD1. When injected with the gene for GPLD1, older mice performed similarly to the active mice on memory tasks and had more neuron growth.

The team looked at the protein in people, too. Older adults who were more active had higher levels of GPLD1 in their blood than inactive adults. Because GPLD1 is produced in the liver, more research is needed to determine how it works on the brain. This research could lead to ways to treat or protect against age-related decline in the brain.

“Through this protein, the liver is responding to physical activity and telling the old brain to get young,” says Dr. Saul Villeda, of the University of California, San Francisco, who led the study.

Abstract:

“Reversing brain aging may be possible through systemic interventions such as exercise. We found that administration of circulating blood factors in plasma from exercised aged mice transferred the effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma concentrations of glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (Gpld1), a GPI-degrading enzyme derived from liver, were found to increase after exercise and to correlate with improved cognitive function in aged mice, and concentrations of Gpld1 in blood were increased in active, healthy elderly humans. Increasing systemic concentrations of Gpld1 in aged mice ameliorated age-related regenerative and cognitive impairments by altering signaling cascades downstream of GPI-anchored substrate cleavage. We thus identify a liver-to-brain axis by which blood factors can transfer the benefits of exercise in old age.”