title: Are aberrant phase transitions a driver of cellular aging?
abstract: Why do cells age? Recent advances show that the cytoplasm is organized into many membrane-less compartments via a process known as phase separation, which ensures spatiotemporal control over diffusion-limited biochemical reactions. Although phase separation is a powerful mechanism to organize biochemical reactions, it comes with the trade-off that it is extremely sensitive to changes in physical-chemical parameters, such as protein concentration, pH, or cellular energy levels. Here, we highlight recent findings showing that age-related neurodegenerative diseases are linked to aberrant phase transitions in neurons. We discuss how these aberrant phase transitions could be tied to a failure to maintain physiological physical-chemical conditions. We generalize this idea to suggest that the process of cellular aging involves a progressive loss of the organization of phase-separated compartments in the cytoplasm.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany. alberti@mpi-cbg.de.
authors.forename: Simon
authors.initials: S
authors.lastname: Alberti
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany. hyman@mpi-cbg.de.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Hyman
mesh_terms: D000818:Animals; D002451:Cell Compartmentation; D016922:Cellular Senescence; D006801:Humans; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D044367:Phase Transition
keywords: aging; amyotrophic lateral sclerosis; chaperone; intrinsically disordered protein; mitochondria; neurodegeneration; phase separation; protein aggregation; protein quality control