Nucleolar expansion: A biomolecular condensate mortality timer

The nucleolus, the largest membraneless organelle in the cell, is a biomolecular condensate that houses ribosomal DNA (rDNA), facilitates ribosomal subunit assembly, and serves as a dynamic reservoir for numerous unrelated proteins. Aging across eukaryotic species is accompanied by nucleolar expansion, raising the question of whether it is a correlate of aging or a driver of cellular aging. Recent studies suggest that nucleolar expansion may drive aging and this may result from age-associated changes in the biophysical properties of the nucleolus. Emerging evidence points to age-driven biophysical changes in the nucleolar condensate, including shifts in size, dynamics, and viscoelasticity, which may occur gradually or through transitions from a liquid-like state to denser gel-like, and in some contexts amyloid-like, assemblies. These transitions remodel two core condensate properties: compartmentalization and partitioning, with consequences for ribosome biogenesis and rDNA stability. Here, we review recent literature on age-driven changes in nucleolar condensation and discuss how these changes may influence nucleolar function and longevity.