Slowing Aging Slows Parkinson's Development, Even When Caused By Genetic Mutations
In some patients Parkinson's disease is associated with genetic variants, most likely because those differences increase susceptibility to damage in the small but critical population of neurons that are destroyed as the disease progresses. It is all very much a matter of levels of damage, however, and so we shouldn't be surprised to see that established methods of modestly slowing aging in laboratory animals also slow the progression of Parkinson's-like model conditions created through genetic alteration. Aging, after all, is also a matter of accumulating damage - the less damage you have, the less aged, dysfunctional, and frail you are.
Scientists have shown in disease models that slowing aging reduces degeneration related to Parkinson's. "It is unknown why symptoms take many decades to develop when inherited mutations that cause the disease are present from birth. Aging is the greatest risk factor for developing Parkinson's - we believe changes that occur during the aging process make brain cells more susceptible to disease-causing mutations that don't cause issues in younger people."In the brain, Parkinson's is marked by the dysfunction and death of the nerve cells that produce dopamine - a chemical that plays a key role in many important functions, including motor control. Clumps of a protein called alpha-synuclein also are found in brain cells of most people with Parkinson's, although scientists are still trying to pin down their exact role. As part of their search for ways to prevent the disease, researchers delayed the aging process in genetic models of Parkinson's disease. They demonstrated that slower aging imparts protection against the loss of dopamine-producing cells in the brain and decreases the formation of alpha-synuclein clumps - both hallmark features of Parkinson's. "This work suggests that slowing aging can have protective effects on the brain cells that otherwise may become damaged in Parkinson's. Our goal is to translate this knowledge into therapies that slow, stop or reverse disease progression."
The team used the worm Caenorhabditis elegans as a genetic model for Parkinson's. Thanks to its simple and well-mapped nervous system, and the ease of genetic manipulation and maintenance of the worm, C. elegans is well-suited for the identification of novel treatment strategies for neurodegenerative diseases. Worm models of Parkinson's disease that expressed either a mutated LRRK2 gene or a mutated alpha-synuclein gene - both of which cause Parkinson's - were crossed with a long-lived strain of the worm to create two new strains with longer lifespans. The researchers found that long-lived LRRK2 and alpha-synuclein worms lost dopamine neurons at a much slower rate than their counterparts with normal lifespans. In fact, the long-lived LRRK2 worms had more dopamine neurons left on day 30 of the study than the LRRK2 worms with a normal lifespan of three weeks had on day eight of adulthood. Slowing aging also effectively reduced motor deficits related to the loss of dopamine-producing cells and eliminated the increased sensitivity to stress shown by worms with a normal lifespan.
The short lived worm were crossed with long lived worms, and the created new strain were with longer lifespan. Theoretically, these genes involved in this study are not genetic interaction. That means LRRK2 and daf2 might impact the lifespan independently. The multiple manipulation of gene activities should be the best way to defeat aging. But, the current strategy for determination of the genetic interaction between genes is really at slow tempo. In my opinion, the biological experiments should be re-innovated and the algorithm for determination of genetic interactions should be established.