Scientists recently launched an innovative study to try to discover whether there is a link between neurodegenerative (brain deterioration) diseases, such as Alzheimer’s disease, aging, and longevity. So, they examined a gene called Cdk5, (in mutant flies) which appeared to speed up aging, promote neurodegeneration, and shorten longevity. Humans also have the CdK5 gene, which is responsible for the genetic information required for the body to build specific proteins.

CdK5 Alterations in Fly Studies

Altering the Cdk5 gene appeared to increase the aging process in flies, making them walk, and fly more problematically later in life, while promoting brain deterioration and early death. The flies with the altered genes were older than their real chronological age.

Researchers discovered in the study that eliminating or increasing the Cdk5 activity, reduced the ability of the flies to climb, caused them to develop neurodegeneration (and brain cell death) and shortened the lives of the flies by approximately 30 days.

“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.”

Flies live, on average, about 47 days. Dr. Giniger and his research team measured the levels of genes at various time spans (10 days, 30 days, etc.) during the life of the flies. This allowed the scientists to utilize some advanced research techniques to analyze which genes were the most sensitive to the aging process.

At the 10-day mark, the mutant flies were compared to the standard curve that the scientists had created as part of the experiment. They found that the flies that had the Cdk5 genes altered appeared older than the control group of 10-day old flies. The brains in the older group of flies (the ones with altered Cdk5 genes) were chronologically about 15 days old, and the bodies were 20 days old.

Interestingly, the Cdk5 gene appears to be a gene that is involved in the development of neurodegenerative disorders such as Parkinson’s disease, ALS and Alzheimer’s disease.

As the researchers continued to study the mutant flies, they discovered that by altering the Cdk5 genes, several other groups of genes were adversely affected as well, including, genes that control the immune system, those that influence one’s energy level, as well as genes that are involved in antioxidant activity.

The researchers evaluated the flies’ antioxidant defenses on free radicals (toxic chemicals found in the cells). As the mutant flies aged, they were gradually more and more unable to fight off the free radicals (living only about 100 hours after exposure to the toxins). The defenses of Cdk5 mutant flies were weaker and they died even 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 disorders.”

Conclusion

More research is required to continue testing the exact role that genetics plays in aging and neurodegeneration; but the initial fly studies may be the beginning of how scientists will be able to manipulate the genes and control aging in the future.


Resources

Science Daily. (2018, March).
https://www.sciencedaily.com/releases/2018/03/180314092253.htm