Liquid-liquid phase separation: A new perspective to understanding aging and pathogenesis

Abstract

Mounting evidence has suggested that phase separation, and especially liquid-liquid phase separation (LLPS), underlies the formation of membraneless organelles, which are supramolecular assemblies of proteins and RNA molecules in cells. These membraneless organelles are also called biomolecular condensates. Evidence is now growing that condensates, such as stress granules, P bodies, Cajal bodies, and nucleoli, play vital roles in biological processes, like RNA storage and processing, signaling regulation, transcription regulation, gene regulation, and transport. Conversely, condensates may cause diseases, such as neurodegenerative diseases and tumors, when they go wrong. Condensates initially have liquid-like properties, but accumulating biological and chemical mutations with age render them into a more solid-like state, like amyloids in Alzheimer's disease, Huntington's disease, and Parkinson's disease. Research into phase separation is still in its infancy, but this field is a promising avenue for treatment of aging-related diseases.