Liquid-liquid phase separation in aging: Novel insights in the pathogenesis and therapeutics

The intricate organization of distinct cellular compartments is paramount for the maintenance of normal biological functions and the orchestration of complex biochemical reactions. These compartments, whether membrane-bound organelles or membraneless structures like Cajal bodies and RNA transport granules, play crucial roles in cellular function. Liquid-liquid phase separation (LLPS) serves as a reversible process that elucidates the genesis of membranelles structures through the self-assembly of biomolecules. LLPS has been implicated in a myriad of physiological and pathological processes, encompassing immune response and tumor genesis. But the association between LLPS and aging has not been clearly clarified. A recent advancement in the realm of aging research involves the introduction of a new edition outlining the twelve hallmarks of aging, categorized into three distinct groups. By delving into the role and mechanism of LLPS in the formation of membraneless structures at a molecular level, this review encapsulates an exploration of the interaction between LLPS and these aging hallmarks, aiming to offer novel perspectives of the intricate mechanisms underlying the aging process and deeper insights into aging therapeutics. •LLPS elucidates the genesis of membranelles structures and participates in various cellular activities.•LLPS is associated with the aging process.•As the twelve hallmarks of aging are elucidated, the mechanism of LLPS in aging becomes clearer.•By regulating the formation of aging hallmarks, LLPS plays a cascading role in aging.•Therapeutic options exist for intervene in LLPS to reverse the aging process and treat aging-associated diseases.