Noncoding Transcriptional Landscape in Human Aging

Abstract

Aging is a universal phenomenon in metazoans, characterized by a general decline of the organism physiology associated with an increased risk of mortality and morbidity. Aging of an organism correlates with a decline in function of its cells, as shown for muscle, immune, and neuronal cells. As the DNA content of most cells within an organism remains largely identical throughout the life span, age-associated transcriptional changes must be achieved by epigenetic mechanisms. However, how aging may impact on the epigenetic state of cells is only beginning to be understood. In light of a growing number of studies demonstrating that noncoding RNAs can provide molecular signals that regulate expression of protein-coding genes and define epigenetic states of cells, we hypothesize that noncoding RNAs could play a direct role in inducing age-associated profiles of gene expression. In this context, the role of long noncoding RNAs (lncRNAs) as regulators of gene expression might be important for the overall transcriptional landscape observed in aged human cells. The possible functions of lncRNAs and other noncoding RNAs, and their roles in the regulation of aging-related cellular pathways will be analyzed.

Long Non-Coding RNAs: A Novel Paradigm for Toxicology

“…Aging is a complex physiological process with a progressive decline of adaptation and functional capacities in multiple organs of the body. The expression of many lncRNAs is affected during different types of senescence, and many lncRNAs govern the major senescent pathways such as p53/p21, pRB/p16, as well as the senescence-associated secretory phenotype (Abdelmohsen and Gorospe, 2015;Costa et al, 2016;Grammatikakis et al, 2014;Kim et al, 2016;Montes and Lund, 2016). This subsequently alters the status of aging in essential metabolic organs such as the heart and nervous system (Devaux et al, 2015;Greco et al, 2015;Szafranski et al, 2015).…”

Competing Endogenous RNAs, Non-Coding RNAs and Diseases: An Intertwined Story

“…Beside the most famous RNA subtypes, such as coding messenger RNAs (mRNAs), transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), recent research has taken a particular interest in pseudo-genes ( -genes), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) [ 6 ]. The non-coding elements have been shown to represent one of the largest portions of transcribed molecules [ 12 , 13 , 14 , 15 ], and to be involved in a very broad set of biological processes [ 16 , 17 , 18 , 19 ], cell-fate programming [ 20 ], aging [ 21 , 22 ] and diseases [ 23 ].…”

RNA Sequencing and Bioinformatics Analysis Implicate the Regulatory Role of a Long Noncoding RNA-mRNA Network in Hepatic Stellate Cell Activation

“…These results indicated that NONRATT013819.2- Lox co-expression and possible interaction might promote HSC transformation and proliferation by activating signaling pathways associated with ECM remodeling. However, the function of lncRNA in liver fibrosis and related mechanisms remains to be confirmed, given that a single lncRNA might potentially regulate the expression of multiple protein-coding genes at diverse levels [36]. Therefore, additional evidence regarding the cross-talk between NONRATT013819.2 and Lox remains to be experimentally validated in our future work.…”