Researchers from Shanghai Institute of Nutrition and Health (SINH) of the Chinese Academy of Science (CAS) and Peking University have found lncRNAs as novel aging markers and regulators, and aging associated lncRNAs carry the signature of evolutionary constraint and participate the NFκB signaling. The study was published in the journal Nature Aging.

Aging is an inevitable process in organism. It causes human tissue and organ degeneration and increases the risk of mortality and diseases. Compared to a century ago, humans are now enjoying greatly improved life quality, medical resources and much more extended lifespan expectancy. However, longer lifespan also increases the risk of chronic disease, reduce perception, motor and cognitive function in old age.

The research team led by Prof. Jing-Dong Jackie HAN from SINH in this study analyzed aging associated transcriptome data of 11 species through bioinformatics methods, and found that aging associated lncRNAs have strong evolutionary conservation and are enriched in functional features documented in various databases. 

From transcription factor binding enrichment and functional prediction, they found that aging associated lncRNAs are predominantly related to NFkB signaling.

By using CRISPR screening, they found 13 of them modulate the reporter of NFkB signaling, and named them NFkB modulating aging-related lncRNAs (NFKBMARL).  

The researchers further studied the molecular mechanisms by which NFKBMARL-1 regulates NFkB signaling.

They found that NFKBMARL-1 binds to the enhancer of its neighboring gene NFKBIZ, a known NFkB mediator and effector, and recruits RELA to the promoter of NFKBIZ within same topological associated domain to amplify NFkB signaling. Inhibiting NFKBMARL-1 inhibits the NFkB signaling and suppresses the expression of aging-related inflammatory factors.

The researchers hope that many more aging-associated lncRNAs can be uncovered as regulators of inflammation, aging and senescence in the future, which highlights them as a previously overlooked key player driving the vicious cycle of 'inflammaging' and underlying the etiology of many aging-associated diseases.