Scientists have long known that being obese increases the risk of dementia and Alzheimer's disease. What remains unclear is how that risk develops in the brain.
Virginia Tech neuroscientist Timothy Jarome is investigating whether obesity may be accelerating the brain's aging process, contributing to earlier memory decline.
The stakes are significant: About one in three adults over 70 experiences age-related memory loss, a condition with no treatment, while nearly 40 percent of U.S. adults are obese.
Jarome, professor in the College of Agriculture and Life Sciences' School of Animal Sciences studies the molecular mechanisms behind memory disorders such as dementia, Alzheimer's disease, and post-traumatic stress disorder (PTSD). His latest research is supported by a $410,000 grant from the National Institute on Aging.
We know obesity affects memory, and we know aging affects memory. What we don't know is whether they're driven by the same process in the brain."
Timothy Jarome, neuroscientist, Virginia Tech
If the two conditions are driven by the same pathway, it could reveal a new target for treatments designed to slow memory loss and reduce dementia risk.
A surprising pattern
In earlier research, Jarome's team found that a molecular process called K63 polyubiquitination becomes more active as memory declines. K63 helps regulate how memories form during learning. In younger brains, K63 levels drop during learning to help memories form. In older brains, those levels stay too high instead of adjusting normally.
When the researchers lowered K63 levels using a targeted gene-editing technique, they were able to improve memory in older rats.
A similar pattern appeared when Jarome and his team looked at young rats fed a high-fat diet. The rats showed elevated K63 levels comparable to those seen in much older rats and performed worse on memory tests.
"What surprised us was we were seeing the same changes in young obese rats that we normally see in much older brains - just on a much faster time scale," Jarome said. "It suggested that obesity-induced memory loss and age-related memory loss may be directly connected through this pathway."
A potential treatment target
The new study will follow rats fed either a high-fat or normal diet from young adulthood through old age, tracking memory changes and whether obesity and aging affect the same proteins in the brain.
Researchers also will use a targeted CRISPR-based tool to reduce K63 levels before obesity develops. The goal is to determine whether the same process that improved memory in older rats can also help prevent memory decline linked to obesity and aging.
Their findings could point toward new treatments designed to slow or prevent memory decline.
"If we can understand the mechanism that connects these two things, then we can start thinking about ways to target it," Jarome said. "My hope is that this will help us better understand what's causing the brain to essentially age faster and make us more likely to have dementia and Alzheimer's disease."
New study reveals how brain cells cause aneurysm ruptures