Signature changes in the expressions of protein-coding genes, lncRNAs, and repeat elements in early and late cellular senescence.

Gökhan Karakülah,Cihangir Yandim

doi:10.3906/biy-2005-21

Abstract

Replicative cellular senescence is the main cause of aging. It is important to note that early senescence is linked to tissue regeneration, whereas late senescence is known to trigger a chronically inflammatory phenotype. Despite the presence of various genome-wide studies, there is a lack of information on distinguishing early and late senescent phenotypes at the transcriptome level. Particularly, the changes in the noncoding RNA portion of the aging cell have not been fully elucidated. By utilising RNA sequencing data of fibroblasts, hereby, we are not only reporting changes in gene expression profiles and relevant biological processes in the early and late senescent phenotypes but also presenting significant differences in the expressions of many unravelled long noncoding RNAs (lncRNAs) and transcripts arisen from repetitive DNA. Our results indicate that, in addition to previously reported L1 elements, various LTR and DNA transposons, as well as members of the classical satellites including HSAT5 and α-satellites (ALR/Alpha), are expressed at higher levels in late senescence. Moreover, we revealed finer links between the expression levels of repeats with the genes located near them and known to be involved in cell cycle and senescence. Noncoding elements reported here provide a new perspective to be explored in further experimental studies.

Highlights

Aging is a natural process that is associated with many health issues, including—but not limited to— cardiovascular problems, neurodegenerative disorders, diabetes, liver disease, and cancer (Lopez-Otin et al, 2013)
And late senescence phenotypes differ in their transcriptomes globally We analysed RNA-seq data from three biological replicates of young proliferating, early senescent, and late senescent LF1 human lung fibroblast cells (Supplementary Tables S1 and S2)
The high number of diseases associated with age and the cellular senescence, including cancer and neurodegenerative disorders, and the fine-tuned balance in which early senescence is adjusted for tissue regeneration and development, while late senescence is disease-inducing, bring about the need for revealing the finer details of this phenomenon

Summary

Introduction

Aging is a natural process that is associated with many health issues, including—but not limited to— cardiovascular problems, neurodegenerative disorders, diabetes, liver disease, and cancer (Lopez-Otin et al, 2013). The decline of proper immune function with age was reported against infections, including the infection caused by the novel coronavirus SARS-Cov-2 (Nikolich-Zugich et al, 2020). Even though the decline of functional tissue with age could be associated with the exposure to many external drivers such as inflammatory or genotoxic factors, cell division itself emerges as the main natural cause of aging. Cellular senescence is characterised by distinct changes in the cell’s cytological and nuclear architecture, as well as the factors that it is releasing to its environment.

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Conclusion