Long Non-Coding RNAs in Neuronal Aging

Abstract

The expansion of long non-coding RNAs (lncRNAs) in organismal genomes has been associated with the emergence of sophisticated regulatory networks that may have contributed to more complex neuronal processes, such as higher-order cognition. In line with the important roles of lncRNAs in the normal functioning of the human brain, dysregulation of lncRNA expression has been implicated in aging and age-related neurodegenerative disorders. In this paper, we discuss the function and expression of known neuronal-associated lncRNAs, their impact on epigenetic changes, the contribution of transposable elements to lncRNA expression, and the implication of lncRNAs in maintaining the 3D nuclear architecture in neurons. Moreover, we discuss how the complex molecular processes that are orchestrated by lncRNAs in the aged brain may contribute to neuronal pathogenesis by promoting protein aggregation and neurodegeneration. Finally, this review explores the possibility that age-related disturbances of lncRNA expression change the genomic and epigenetic regulatory landscape of neurons, which may affect neuronal processes such as neurogenesis and synaptic plasticity.

Cellular Aging Characteristics and Their Association with Age-Related Disorders

“…Additionally, lncRNAs have been shown to contribute to neuronal pathogenesis [67] through the modulation of gene expression in the central nervous system [68].…”

“…In this context, SIRT3 acted as a neuroprotective molecule and mitigated stress condition effects. Moreover, the investigation showed that the downregulation of SIRT3 decreased the activity of metabolic enzyme complex I and ATP levels [67].…”

Biomarker expression analysis in different age groups revealed age was a risk factor for breast cancer

“…Belonging to the family of noncoding RNAs, lncRNAs have been shown to be essential in the development and differentiation of normal cells and tissues as well as in the initiation and progression of various pathogenic conditions, especially cancer (Khorkova, Hsiao, & Wahlestedt, 2015). Recent studies have suggested that there are age-dependent variations in lncRNA expression profiles (Arshi et al, 2018;Pereira Fernandes, Bitar, Jacobs, & Barry, 2018). Analyses of the molecular processes involved in some age-related phenotypes have provided compelling evidence confirming that lncRNAs are indeed key regulators in the manifestation of these phenotypes (Grammatikakis, Panda, Abdelmohsen, & Gorospe, 2014;Kour & Rath, 2016).…”

Emerging Roles of Long Non-Coding RNAs as Drivers of Brain Evolution

“…This number is remarkably high considering the approximately 20,000-25,000 protein-coding genes [8] and argues for widespread functional implications. In support of this, lncRNAs show precise regional, cellular and subcellular expression patterns in the brain, which underlie dynamic remodeling during brain development [9][10][11][12], in response to neuronal activity [13][14][15] and during brain aging [16].…”