To understand the link between aging and neurodegenerative disorders such as Alzheimer’s disease, scientists from the National Institutes of Health compared the genetic clocks that tick during the lives of normal and mutant flies. They found that altering the activity of a gene called Cdk5 appeared to make the clocks run faster than normal, and the flies older than their chronological age. This caused the flies to have problems walking or flying later in life, to show signs of neurodegeneration, and to die earlier.
“We tried to untangle the large role aging appears to play in some of the most devastating neurological disorders,” said Edward Giniger, Ph.D., senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke and the senior author of the study published in Disease Models & Mechanisms. “Our results suggest that neurodegenerative disorders may accelerate the aging process.”
On average, the normal flies in this study lived for 47 days. To create a genetic clock, Dr. Giniger’s team measured the levels of every gene encoded in messenger RNA molecules from cells from the heads and bodies of flies at 3, 10, 30, and 45 days after birth. This allowed the researchers to use advanced analysis techniques to search for the genes that seemed to be sensitive to aging, and create a standard curve, or timeline, that described the way they changed.
When they performed the same experiments on 10-day-old mutant flies and compared the results with the standard curve, they found that the flies were “older” than their chronological age. Altering Cdk5 activity made the brains of the flies appear genetically to be about 15 days old and their bodies to be about 20 days old.