Taking out the protein garbage becomes more difficult as neurons age

As cells age, their ability to remove damaged proteins and structures declines, which could be a risk factor for neurodegenerative brain diseases.

Cells dispose of harmful “trash” through autophagy, a normal and necessary process in which aggregated proteins and dysfunctional structures are handled. If any part of this fails, waste builds up inside cells, eventually killing them. According to a new study from the Perelman School of Medicine as cells age, their ability to shed harmful refuse declines. The findings suggest that the deterioration of autophagy in aged neurons—cells that never replicate and are as old as the bodies they inhabit—could be a risk factor for a suite of neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis), Alzheimer’s, and Parkinson’s.

Eight photos showing a microscopic view of the destruction of neurons in a cell.
Aberrantly formed autophagosomes accumulate in an aged neuron. (Photo: Andrea Stavoe, Penn Medicine; eLife)

Using live-cell imaging of neurons from young and aged mice, Erika Holzbaur, a professor of physiology, and first author Andrea Stavoe, a postdoctoral fellow in Holzbaur’s lab, published their study in eLife

“The current thinking among scientists is that a decline in autophagy makes neurons more vulnerable to genetic or environmental risks,” Holzbaur said. “What motivates our line of research is that most neurodegenerative diseases in which a deterioration of autophagy has been implicated, such as ALS, and Alzheimer’s, Huntington’s and Parkinson’s diseases, are also disorders of aging.”

Read more at Penn Medicine News.