Long non-coding RNAs in aging and aging-associated diseases
Long noncoding RNAs (lncRNAs) are a type of RNA, generally defined as transcripts more than 200 nucleotides that are not translated into protein. LncRNAs are roughly classified based on their position relative to protein-coding genes: intergenic (between genes), intragenic/intronic (within genes) and antisense. Until recently, these RNAs were disregarded as “junk”, due to their inability to produce functional proteins. But it is now evident that these lncRNAs can assume crucial roles in almost every aspect of biology. Most annotated lncRNAs are RNA polymerase II (Pol II) transcribed; hence, they are similar in structure to mRNA and may have cap structures and poly A tails. Unlike protein-coding mRNAs, lncRNAs exhibit functional uniqueness by participating in and modulating the various cellular processes such as, histone modification, DNA methylation, and cellular transcription.
Cardiovascular diseases (CVDs) are currently the main cause of morbidity and mortality. It was found that 145 lncRNAs are differentially expressed in ischemic cardiomyopathy tissues compared with healthy control samples. Thus, overcoming the challenges of determining cardiac-related lncRNAs and their molecular mechanisms may be significantly beneficial to our further investigations in the diagnosis and treatment of CVDs. However, treatment strategies on targeting lncRNA remain difficult to apply to the clinic.  
The endothelial cells that line the vessel walls play an important role in the development of atherosclerosis. Non-coding RNA such as long non-coding RNAs are known to play an important role in endothelial function and are implicated in the disease progression. Of 4465 lncRNAs expressed in the human endothelium, 798 lncRNAs are dysregulated in advanced age. Among these differentially expressed lncRNAs, prostate-cancer-associated transcript 14 (PCAT14), which is localized in the nucleus of young endothelial cells, but significantly reduced in aged endothelium. By silencing PCAT14, it was demonstrated that endothelial cell migration and sprouting capacity were reduced, without affecting the endothelial proliferative capacity. Furthermore, silencing of PCAT14 resulted in increased expression of inflammatory genes (e.g., ICAM1 and SELE) and genes relevant to endothelial cell stalk formation (e.g., JAG1 and ESM1), suggesting that PCAT14 may be important in maintaining the healthy status of the endothelium.
Transcribed-Ultra Conserved Regions (T-UCRs)
The ultraconserved regions (UCRs) are genomic elements longer than 200 bp (range: 200-779 bp) that are absolutely conserved among orthologous regions of human, mouse, and rat genomes. These regions also exhibit extremely high levels of conservation in other species, such as fish, chicken, and fugu, strongly suggesting an extreme negative selection of these sequences. More than 80% of UCRs are intergenic or intronic. The genome-wide profiling reveals that most UCRs are transcriptional active; therefore, these regions are also named transcribed UCRs (T-UCRs). Most T-UCRs may be lncRNAs (long noncoding RNAs), defined as RNAs larger than 200 bp, mostly without coding potential. T-UCRs were associated with different hallmarks and showed great potential as biomarkers in many tumor types.
The studies in the literature about the associations between the presence of SNPs in UCRs and the appearance of different disorders revealed at least 37 polymorphism/phenotype associations covering diseases such as: different types of muscular dystrophies; adolescent idiopathic scoliosis; amyotrophic lateral sclerosis; renal diseases; as well as eye-related diseases; and cancer. For example, the T-UCR uc.323 deficiency induced cardiac hypertrophy since uc.323 regulate the expression of cardiac hypertrophy-related genes such as CPT1b (Carnitine Palmitoyl transferase 1b).
lncRNA participates in multiple aging-related neurological disorders development. Accumulating evidence has implicated lncRNA dysregulation in neurodegenerative disorders, including Alzheimer’s disease, whereby a group of long non-coding RNAs in blood can serve as a specific biomarker of Alzheimer's disease Parkinson’s disease, and Huntington’s disease (Tan et al., 2021)
Long non-coding RNAs and rheumatoid arthritis
Various lncRNAs have proven potential as biomarkers and targets for diagnosing, prognosis and treating rheumatoid arthritis.
Accumulating evidence revealed that the regulatory network that includes long non-coding RNAs (lncRNAs)/circular RNAs (circRNAs), micro RNAs (miRNAs), and messenger RNAs (mRNA) plays important roles in regulating the pathological and physiological processes in rheumatoid arthritis. lncRNAs/circRNAs act as the miRNA sponge and competitively bind to miRNA to regulate the expression mRNA in synovial tissue, fibroblast-like synoviocytes (FLS), and peripheral blood mononuclear cells (PBMCs), participate in the regulation of proliferation, apoptosis, invasion, and inflammatory response.
Role of the lncRNA–miRNA–mRNA Axis in Chronic Inflammatory Airway Diseases
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