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NIH Scientists Identify Genetic Culprit Impacting our Biological Clocks

Aging is the greatest risk factor for neurodegeneration, but the connection between the two processes remains opaque. This is in part for want of a rigorous way to define physiological age, as opposed to chronological age.

Now, in order to understand the link between aging and neurodegenerative disorders such as Alzheimer’s disease, NIH scientists 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.”

Preclinical studies suggest that Cdk5 is a gene that is important for the normal wiring of the brain during early development and may be involved in some neurodegenerative disorders, including ALS, Parkinson’s and Alzheimer’s disease.

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Similarly, the team, in the course of this study, 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.

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,” said Dr. Giniger. “We hope that our approach will help researchers untangle the mysteries behind several neurodegenerative disorders.

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