Altering the activity of a gene called Cdk5 in flies appears to make them 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.
This gene, researchers note from preclinical studies, is important for the normal wiring of the brain during early development and may be involved in some neurological disorders, such as ALS, Parkinson’s, and Alzheimer’s disease.
“We tried to untangle the large role aging appears to play in some of the most devastating neurological disorders,” said Edward Giniger, PhD, 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.”
In the study, Giniger and his team created a genetic clock for the flies used in the study by measuring 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, explains a media release from the National Institutes of Health.
The researchers found that eliminating or increasing Cdk5 activity beyond normal levels shortened the lives of the flies to about 30 days. After 10 days of age, the manipulations reduced the distance flies could climb up tubes and the alterations caused older flies to have signs of neurodegeneration, including higher than normal levels of brain cell death and degradation.
More analysis showed that altering Cdk5 activity changed the level of several groups of genes that were also affected by aging, including those that control immunity, energy, and antioxidant activity.
To explore this idea further, the researchers tested the strength of the flies’ antioxidant defenses against toxic versions of several chemicals found in cells called oxygen free radicals. Initial experiments showed that aging reduced these defenses in normal flies. Three-day-old healthy flies lived for about 100 hours after exposure to free radicals, and that time decreased with age. In contrast, the defenses of Cdk5 mutant flies were even weaker as they died sooner than the control flies at all ages, the release continues.
“Our results suggest that aging may not just predispose an individual to degeneration, as we thought. Acceleration of aging may actually be part of the mechanism by which degenerative disease disrupts the structure and function of the brain,” Giniger says. “We hope that our approach will help researchers untangle the mysteries behind several neurodegenerative disorders.”
[Source: National Institutes of Health]
