Vascular Endothelial Senescence: Pathobiological Insights, Emerging Long Noncoding RNA Targets, Challenges and Therapeutic Opportunities

Abstract

Cellular senescence is a stable form of cell cycle arrest in response to various stressors. While it serves as an endogenous pro-resolving mechanism, detrimental effects ensue when it is dysregulated. In this review, we introduce recent advances for cellular senescence and inflammaging, the underlying mechanisms for the reduction of nicotinamide adenine dinucleotide in tissues during aging, new knowledge learned from p16 reporter mice, and the development of machine learning algorithms in cellular senescence. We focus on pathobiological insights underlying cellular senescence of the vascular endothelium, a critical interface between blood and all tissues. Common causes and hallmarks of endothelial senescence are highlighted as well as recent advances in endothelial senescence. The regulation of cellular senescence involves multiple mechanistic layers involving chromatin, DNA, RNA, and protein levels. New targets are discussed including the roles of long noncoding RNAs in regulating endothelial cellular senescence. Emerging small molecules are highlighted that have anti-aging or anti-senescence effects in age-related diseases and impact homeostatic control of the vascular endothelium. Lastly, challenges and future directions are discussed including heterogeneity of endothelial cells and endothelial senescence, senescent markers and detection of senescent endothelial cells, evolutionary differences for immune surveillance in mice and humans, and long noncoding RNAs as therapeutic targets in attenuating cellular senescence. Accumulating studies indicate that cellular senescence is reversible. A better understanding of endothelial cellular senescence through lifestyle and pharmacological interventions holds promise to foster a new frontier in the management of cardiovascular disease risk.

Endothelial Senescence and the Chronic Vascular Diseases: Challenges and Therapeutic Opportunities in Atherosclerosis

“…On the one hand, this phenotype could be considered an essential activator of an efficient immune response that controls the cellular senescence process. On the other hand, SASP could be one of the primary mechanisms that turn cellular senescence into a physiopathological mechanism in developing age-related diseases [20].…”

Noncoding RNAs in the Glycolysis of Ovarian Cancer

“…LncRNAs are a category of noncoding RNAs with over 200 nucleotides in length, tissue specificity and low species conservation ( Jalaiei et al, 2021 ; Zhao et al, 2021 ). LncRNAs bind to proteins through their unique secondary structure to form RNA-protein complexes ( Dashti et al, 2021 ; Janaththani et al, 2021 ; Mardani et al, 2021 ) and interact with multiple RNAs to form complex gene expression regulatory networks ( Sun and Feinberg 2021 ; Wu et al, 2021 ). LncRNAs also target miRNAs through their 3′UTR region to regulate the effective concentration and activity, which affects the repressive effect on the target mRNAs( Sun and Feinberg 2021 ; Wu et al, 2021 ).…”

Promising Strategies for Preserving Adult Endothelium Health and Reversing Its Dysfunction: From the Liquid Biopsy to New Omics Technologies and Non-invasive Circulating Biomarkers

“…The Abasht group [34] used this approach for evaluating vascular endothelial dysfunction in wooden breast syndrome, while the Treder group [35] used this approach for detecting graft detachment in Descemet membrane endothelial keratoplasty. Furthermore, it is currently being applied to develop algorithms for vascular endothelial senescence, as recently evidenced by Sun and Feinberg [36].…”