Scientists search for the clocks behind aging brain disorders

March 14, 2018 by Christopher G. Thomas, National Institutes of Health

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 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 and compared the results with the standard curve, they found that the flies were "older" than their . 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.

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. In this study, Dr. Giniger's team 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 . 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.

"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 ."

His team plans to continue investigating the role of aging in the process of neurodegeneration.

Explore further: A neuron can cause a domino effect

More information: Joshua Spurrier et al, Altered expression of the Cdk5 activator-like protein, Cdk5α, causes neurodegeneration, in part by accelerating the rate of aging, Disease Models & Mechanisms (2018). DOI: 10.1242/dmm.031161 ,

Related Stories

A neuron can cause a domino effect

March 2, 2018
Loss of the sense of smell can indicate a neural disease like Alzheimer's or Parkinson's disease. However, contrary to previous belief, degenerations in the nervous system do not play a leading role in the loss of the sense ...

Neuroscientists show 'jumping genes' may contribute to aging-related brain defects

April 8, 2013
As the body ages, the physical effects are notable; wrinkles in the skin appear, physical exertion becomes harder. But there are also less visible processes going on. Inside aging brains there is another phenomenon at work, ...

Fruit fly breakthrough may help human blindness research

December 18, 2017
For decades, scientists have known that blue light will make fruit flies go blind, but it wasn't clear why. Now, a Purdue University study has found how this light kills cells in the flies' eyes, and that could prove a useful ...

Link found between MicroRNA and neurological aging in fruit flies

February 16, 2012
(Medical Xpress) -- Researchers from several institutions in the Philadelphia area have banded together to form a team to look into the possible impact a certain type of MicroRNA (miRNA) may have on the neurological aging ...

Recommended for you

Gradual release of immunotherapy at site of tumor surgery prevents tumors from returning

March 21, 2018
A new study by Dana-Farber Cancer Institute scientists suggests it may be possible to prevent tumors from recurring and to eradicate metastatic growths by implanting a gel containing immunotherapy during surgical removal ...

Cold can activate body's 'good' fat at a cellular level, study finds

March 21, 2018
Lower temperatures can activate the body's 'good' fat formation at a cellular level, a new study led by academics at The University of Nottingham has found.

Immune cells in the retina can spontaneously regenerate

March 21, 2018
Immune cells called microglia can completely repopulate themselves in the retina after being nearly eliminated, according to a new study in mice from scientists at the National Eye Institute (NEI). The cells also re-establish ...

Switch discovered to convert blood vessels to blood stem cells in embryonic development

March 20, 2018
A switch has been discovered that instructs blood vessel cells to become blood stem cells during embryonic development in mice. Using single-cell technology, researchers from the Wellcome Sanger Institute in Cambridge and ...

Stem cells treat macular degeneration

March 19, 2018
In July 2015, 86-year-old Douglas Waters developed severe age-related macular degeneration (AMD). He struggled to see things clearly, even when up close.

Don't blame adolescent social behavior on hormones

March 19, 2018
Reproductive hormones that develop during puberty are not responsible for changes in social behavior that occur during adolescence, according to the results of a newly published study by a University at Buffalo researcher.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.