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Background: Immunosenescence is a multifactorial stress response to different intrinsic and extrinsic insults that cause immune deterioration and is accompanied by genomic or epigenomic perturbations. It is now widely recognized that genes and proteins contributing in the process of immunosenescence are regulated by various noncoding (nc) RNAs, including microRNAs (miRNAs), long ncRNAs, and circular RNAs. Aims: This review article aimed to evaluate the regulatore RNAs roles in the process of immunosenescence. Methods: We analyzed publications that were focusing on the different roles of regulatory RNAs on the several aspects of immunosenescence. Results: In the immunosenescence setting, ncRNAs have been found to play regulatory roles at both transcriptional and post‐transcriptional levels. These factors cooperate to regulate the initiation of gene expression programs and sustaining the senescence phenotype and proinflammatory responses. Conclusion: Immunosenescence is a complex process with pivotal alterations in immune function occurring with age. The extensive network that drive immunosenescence‐related features are are mainly directed by a variety of regulatory RNAs such as miRNAs, lncRNAs, and circRNAs. Latest findings about regulation of senescence by ncRNAs in the innate and adaptive immune cells as well as their role in the immunosenescence pathways, provide a better understanding of regulatory RNAs function in the process of immunosenescence. Highlights: The immunosenescence process is strictly controlled by genetic and epigenetic factorsInnate and adaptive immune responses are affected by immunosenescenceThe proteostasis is a major hallmark of aging and cellular senescenceThe regulatory RNAs are involved in the aging of immune system [ABSTRACT FROM AUTHOR]

Immune system is a versatile and dynamic body organ which offers survival and endurance of human beings in their hostile living environment. However, similar to other cells, immune cells are hijacked by senescence. The ageing immune cells lose their beneficial functions but continue to produce inflammatory mediators which draw other immune and non-immune cells to the senescence loop. Immunosenescence has been shown to be associated with different pathological conditions and diseases, among which atherosclerosis has recently come to light. There are common drivers of both immunosenescence and atherosclerosis; e.g. inflammation, reactive oxygen species (ROS), chronic viral infections, genomic damage, oxidized- LDL, hypertension, cigarette smoke, hyperglycaemia, and mitochondrial failure. Chronic viral infections induce inflammaging, sustained cytokine signaling, ROS generation and DNA damage which are associated with atherogenesis. Accumulating evidence shows that several DNA and RNA viruses are stimulators of immunosenescence and atherosclerosis in an interrelated network. DNA viruses such as CMV, EBV and HBV upregulate p16, p21 and p53 senescence-associated molecules; induce inflammaging, metabolic reprogramming of infected cells, replicative senescence and telomere shortening. RNA viruses such as HCV and HIV induce ROS generation, DNA damage, induction of senescence-associated secretory phenotype (SASP), metabolic reprogramming of infected cells, G1 cell cycle arrest, telomere shortening, as well as epigenetic modifications of DNA and histones. The newly emerged SARS-CoV-2 virus is also a potent inducer of cytokine storm and SASP. The spike protein of SARS-CoV-2 promotes senescence phenotype in endothelial cells by augmenting p16, p21, senescence-associated bgalactosidase (SA-b-Gal) and adhesion molecules expression. The impact of SARS-CoV-2 mega-inflammation on atherogenesis, however, remains to be investigated. In this review we focus on the common processes in immunosenescence and atherogenesis caused by chronic viral infections and discuss the current knowledge on this topic. [ABSTRACT FROM AUTHOR]

The relationship between high levels of anti-Varicella Zoster Virus (VZV) IgG in cerebrospinal fluid (CSF) and cerebrovascular atherosclerosis commends a possible similar association in other vessels. We aimed to investigate the association of VZV-seropositivity with coronary artery atherosclerosis. We recruited 88 newly diagnosed patients with more than 50% stenosis in at least one of the main coronary arteries. As the control group, 99 age-matched individuals with normal/insignificant coronary artery findings were included. Clinical, paraclinical, and demographical data were gathered at the time of sampling. High-sensitivity C-reactive protein (hsCRP) levels were measured by nephelometry. VZV-seropositivity was determined by measuring of anti-VZV IgG level in plasma. Multivariable logistic regression was used to evaluate the correlation of data with coronary vascular atherosclerosis. The frequency of VZV-seropositivity was significantly higher in the atherosclerosis group compared to the controls (OR=1.88; 95%CI=1.03-3.44). The plasma levels of anti-VZV IgG were significantly higher in patients with atherosclerosis (Median=2.70, IQR=1.53-4.30 AU/mL) than in the controls (Median=2.10, IQR=1.70-3.10 AU/mL, p=0.034). The hsCRP levels in patients and controls were 5.19±2.00 and 1.51±1.07 mg/L, respectively. The correlation between hsCRP and anti-VZV IgG level in plasma was observed (r=0.40, p<0.001). The levels of hsCRP and anti-VZV IgG increased based on the number of diseased vessels but only the difference in hsCRP levels reached a significant level (p<0.001 and p=0.168, respectively). Our data suggest that VZV-seropositivity and hsCRP elevation jointly increase the risk of atherosclerosis. The multifactorial nature of atherosclerosis; however, leaves more options for the inflammatory milieu to be generated. [ABSTRACT FROM AUTHOR]