The results of a study of mice suggest that therapies that can keep us younger longer might also protect against Alzheimer’s disease.
The researchers found that simply slowing the aging process in mice carrying human genes that cause them to develop Alzheimer’s disease prevented their brains from turning into a neuronal wasteland.
Study leader Andrew Dillin emphasizes that the ultimate aim is to improve the quality of life, not the quantity. “The goal is not to make people live to be 250 years old, it is to delay the onset of sickness,” he said. “I want to find ways to extend health span, not necessarily life span.”
Age is the major risk factor for the development of Alzheimer’s disease. Beyond age 65, the number of people with the disease doubles every five years. Centenarians, however, seem to escape most common age-related diseases, including the ravages of Alzheimer’s disease.
“In this study, we went directly to the root cause of Alzheimer’s disease and asked whether we could influence the onset of the disease by modulating the aging process,” says first author Ehud Cohen.
The researchers slowed the aging process in a mouse model for Alzheimer’s disease by lowering the activity of the IGF-1 signaling pathway. “This highly conserved pathway plays a crucial role in the regulation of lifespan and youthfulness across many species, including worms, flies, and mice and is linked to extreme longevity in humans,” Cohen explains. As a result, mice with reduced IGF-1 signaling live up to 35 percent longer than normal mice.
One of the telltale signs of Alzheimer’s disease is the buildup of toxic clumps of beta amyloid plaques in the brain. Beta amyloid production probably occurs in all brains, but healthy cells clear away excess amounts. Brains of people with Alzheimer’s disease, on the other hand, are unable to control beta amyloid accumulation. The same is true for Alzheimer’s mouse models, which are genetically engineered to overproduce beta amyloid.
The brains of the mice that were spared the cognitive, inflammatory and neural effects of Alzheimer’s disease by reducing the IGF-1 signaling pathway were still riddled with amyloid plaques. However, those plaques were more tightly packed into larger clusters than they would otherwise have been. Although the brains of the long-lived mice were riddled with highly compacted plaques, they didn’t show any of the cognitive or behavioral impairments typical of Alzheimer’s disease till very late in life.
Image: Top: This is beta amyloid plaque as it appears in normally aging Alzheimer’s mice. Bottom: This is tighter packed plaques in long-lived Alzheimer’s mice protect against the disease.
References:
1. Andrew Dillin, et al. Reduced IGF-1 Signaling Delays Age-Associated Proteotoxicity in Mice. Cell, Volume 139, Issue 6, 1157-1169, 11 December 2009. doi:10.1016/j.cell.2009.11.014
2. Image courtesy of Dr. Ehud Cohen, Hebrew University-Hadassah Medical School
