Cells undergo natural aging and death, processes that impact a multitude of factors. A Stony Brook (N.Y.) University-led study published in PNAS provides a biophysical model that reveals how damage accumulates in the shapes of cellular proteins with age and is a trigger to death. The finding opens a door to a better understanding of the molecular origins of age-related neurodegenerative diseases, such as Alzheimer's and Parkinson's, which all entail protein damage.
Young cells are kept healthy by the positive processes of protein synthesis, degradation, and keeping proteins properly folded (called chaperoning). As cells age, negative processes increase, reducing proteins' ability to fold. One of these negative processes is oxidative damage, which the research team focuses on in the model. Once negative processes exceed positive ones, protein misfolding becomes rampant and cell death occurs.
Coauthor Ken A. Dill, Distinguished Professor and director of the Center for Physical & Quantitative Biology, says that the research team developed a Proteome Collapse Model that explores a central question in biology: how does the folding health of proteomes (collection of all the cell's proteins) change with damage and age?