Suppressing a cellular cleanup-mechanism known as autophagy can accelerate the accumulation of protein aggregates that leads to neural degeneration.
In an upcoming issue of Autophagy, scientists at the Salk Institute for Biological Studies report for the first time that the opposite is true as well: Boosting autophagy in the nervous system of fruit flies prevented the age-dependent accumulation of cellular damage in neurons and promoted longevity.
“We discovered that levels of several key pathway members are reduced in Drosophila neural tissue as a normal part of aging,” says senior author Kim Finley, Ph.D., a scientist in the Cellular Neurobiology Laboratory, “which suggests there is an age-dependent suppression of autophagy that may be a contributing factor for human neurodegenerative disorders like Alzheimer's disease.”
As the American population grows older, questions regarding the aging process and how it can be positively influenced are increasingly becoming the focus of scientific research and public interest. The age-related accumulation of proteins and lipids damaged by chemically aggressive forms of oxygen is considered by most in the geriatrics field to be a normal part of the aging process. As a result in most age-associated diseases, such as Alzheimer's, damaged proteins accumulate in excessive amounts, which leads to progressive cell death in the brain.
All cells undergo autophagy - literally self-eating, - which requires the assembly of specialized vesicles called autophagosomes. These vesicles surround or engulf damaged cellular proteins or structures and then traffic the “bagged garbage” to a second group of vesicles, which disposes of the trash with the help of digestive enzymes. This process can be enhanced when animals are placed on a calorie-restricted diet, a regime known to extend lifespan.
“The activation of autophagy facilitates the removal of damaged molecules that accumulate during cellular aging,” says Finley. “This may be particularly important in the nervous system since neurons produce damaged molecules at a much higher rate than most cell types.” Keeping cells free of damaged molecules is critical for neurons because unlike many cells, they do not divide or replace themselves once created at birth. “They rely on autophagy together with other clearance and detoxification pathways to keep themselves healthy and functioning for decades,” explains Finley.