Work

Proteostasis collapse is a driver of cell aging and death

Year: 2019

Type: article

Abstract: Significance Cells and organisms grow old and die. We develop a biophysical model of the mechanism. Young cells are kept healthy by the positive processes of protein synthesis, degradation, and chaperoning (the activity of keeping proteins properly folded). But, with age, negative processes increase: Oxidative damage accumulates randomly in the cell’s proteins, healthy synthesis and degradation slow down, and—like overfilled garbage cans—chaperone capacity is exceeded. The chaperones are distracted trying to fold irreversibly damaged proteins, leading to accumulating misfolded and aggregated proteins in the cell. The tipping point to death happens when the negative overwhelms the positive. The model makes several quantitative predictions of the life span of the worm Caenorhabditis elegans .

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1906592116

Authors: Mantu Santra, Ken A. Dill, Adam M. R. de Graff

Institutions: Stony Brook School, Stony Brook University, S.N. Bose National Centre for Basic Sciences

Language: English

Topic: Genetics, Aging, and Longevity in Model Organisms

Subfield: Aging

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Funder: Division of Biological Infrastructure

Award: G2004148766