Aging-associated lncRNAs are evolutionarily conserved and participate in NFκB signaling

Aging, inflammation and senescence are controlled by NF kappa B. Cai and Han identify by comparative genomics a family of lncRNAs that are increasingly expressed during aging by NF kappa B-driven transcription, and find that many of these aging-associated lncRNAs regulate NF kappa B activity in turn. The transcriptome undergoes global changes during aging, including both protein-coding and noncoding RNAs. Using comparative genomics, we identify aging-associated long noncoding RNAs (lncRNAs) that are under evolutionary constraint and are more conserved than lncRNAs that do not change with age. Aging-associated lncRNAs are enriched for functional elements, including binding sites for RNA-binding proteins and transcription factors, in particular nuclear factor kappa B (NF kappa B). Using CRISPR screening, we discovered that 13 of the aging-associated lncRNAs were regulators of the NF kappa B pathway, and we named this family 'NF kappa B modulating aging-related lncRNAs (NFKBMARLs)'. Further characterization of NF kappa BMARL-1 reveals it can be traced to 29 Ma before humans and is induced by NF kappa B during aging, inflammation and senescence. Reciprocally, NF kappa BMARL-1 directly regulates transcription of the NF kappa B inhibitor NFKBIZ in cis within the same topologically associated domain by binding to the NFKBIZ enhancer and recruiting RELA to the NFKBIZ promoter. These findings reveal many aging-associated lncRNAs are evolutionarily conserved components of the NF kappa B pathway.

Automated summary

NF kappa B controls aging, inflammation, and senescence by regulating an increasing family of lncRNAs. These aging-associated lncRNAs are enriched for functional elements and play a role in aging process by modulating the NF kappa B pathway.