Age is a hindrance to autophagy
Cells get rid of harmful "garbage" for them through the process of autophagy. If any part of the process fails, the waste accumulates inside the cells, eventually killing them. With age, the ability to process harmful waste decreases. The data obtained during a study conducted at the University of Pennsylvania indicate that the deterioration of the autophagy process in neurons may be a risk factor for the development of a number of neurodegenerative diseases, such as amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson's disease. Currently, it is also believed that the deterioration of the quality of the autophagy process makes neurons more vulnerable to genetic or environmental risk factors.
The importance of the autophagy process for the body was noted in 2016 with the Nobel Prize in Physiology or Medicine.
At the beginning of the process, a cellular organoid called an autophagosome absorbs improperly folded proteins or damaged parts of the cell, isolating these wastes in a structure resembling a garbage bag. The autophagosome then merges with the lysosome, which contains the enzymes needed to break down the debris, allowing the components to be recycled and reused. Such an uncomplicated process ensures the health of neurons, but with its violations they die.
The scientists evaluated the frequency of autophagy in mouse neurons during aging and revealed a significant decrease in the number of autophagosomes produced, as well as obvious defects in their structure.
The early stages of autophagosome formation were unchanged, but there were frequent delays in their formation, and those autophagosomes that were still formed were deformed. Such defects lead to the accumulation of toxic structures in the synapses of neurons. In other studies of the process, autophagosomes with improperly formed membranes could be found in dead people in brain tissues obtained from donors with neurodegenerative diseases.
It is also important to note that the inclusion of the WIPI2B protein in old mice restores the formation of autophagosomes in neurons, returning the garbage disposal process to a working state. At the same time, when scientists turned off the protein in the neurons of young mice, the formation of autophagosomes stopped. According to scientists, WIPI2B represents a new target for the treatment of age-related neurodegeneration.
The article Stavoe et. al Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons is published in the journal eLife.
Elena Panasyuk, portal "Eternal Youth" based on Penn Medicine News: Taking out the Protein Garbage Becomes More Difficult as Neurons Age