LncRNAs: the missing link to senescence nuclear architecture.

During cellular senescence and organismal aging, cells display various molecular and morphological changes. Although many aging-related long noncoding RNAs (lncRNAs) are highly associated with senescence-associated secretory phenotype, the roles of lncRNAs in senescence-associated nuclear architecture and morphological changes are just starting to emerge. Here I review lncRNAs associated with nuclear structure establishment and maintenance, their aging-related changes, and then focus on the pervasive, yet underappreciated, role of RNA double-strand DNA triplexes for lncRNAs to recognize targeted genomic regions, making lncRNAs the nexus between DNA and proteins to regulate nuclear structural changes. Finally, I discuss the future of deciphering direct links of lncRNA changes to various nuclear morphology changes assisted by artificial intelligence and genetic perturbations.