Since genome (chromosome) instability may result from viral infections (Heng, 2019), SARS-CoV-2 interactions with cells of the central nervous system are able to increase the risk for early manifestations of aging-related brain disorders and/or premature brain deterioration mediated by genome and chromosome instability. Here, we have addressed data on SARS-CoV-2-host protein-protein interactomes for assessing potential COVID-19 effects on aging-related genome (chromosome) instability in the brai

Iourov, I. Y.

Vorsanova, S. G.

PubMed

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OPINIONpublished: 03 March 2022doi: 10.3389/fnagi.2022.786264Frontiers in Aging Neuroscience | www.frontiersin.org 1 March 2022 | Volume 14 | Article 786264Edited by:Julia Fuchs,Institut National de la Santé et de laRecherche Médicale(INSERM), FranceReviewed by:Henry H. Q. Heng,Wayne State University, United States*Correspondence:Ivan Y. Iourovivan.iourov@gmail.comSpecialty section:This article was submitted toNeuroinflammation and Neuropathy,a section of the journalFrontiers in Aging NeuroscienceReceived: 30 September 2021Accepted: 31 January 2022Published: 03 March 2022Citation:Iourov IY and Vorsanova SG (2022)COVID-19 and Aging-RelatedGenome (Chromosome) Instability inthe Brain: Another PossibleTime-Bomb of SARS-CoV-2 Infection.Front. Aging Neurosci. 14:786264.doi: 10.3389/fnagi.2022.786264COVID-19 and Aging-RelatedGenome (Chromosome) Instability inthe Brain: Another PossibleTime-Bomb of SARS-CoV-2 InfectionIvan Y. Iourov 1,2,3* and Svetlana G. Vorsanova 1,21 Yurov’s Laboratory of Molecular Genetics and Cytogenomics of the Brain, Mental Health Research Center, Moscow, Russia,2 Laboratory of Molecular Cytogenetics of Neuropsychiatric Diseases, Veltischev Research and Clinical Institute for Pediatricsof the Pirogov Russian National Research Medical University, Moscow, Russia, 3Department of Medical BiologicalDisciplines, Belgorod State University, Belgorod, RussiaKeywords: aging, brain, chromosome instability, COVID-19, neurodegeneration, genome instability, SARS-CoV-2It is hard to estimate the profound impact of COVID-19 (SARS-CoV-2 infection) on ourlife. SARS-CoV-2 infection is the cause of a pandemic and is associated with a severe diseasethreatening life during and after the manifestation (Tu et al., 2020; Wu et al., 2020; Hu et al.,2021). It is repeatedly noted that the central nervous system is seriously affected by COVID-19infection. However, the intrinsic effects of COVID-19 on the human brain remain a matter offuture research (Pennisi et al., 2020). Pathological brain aging and natural brain deteriorationare associated with accumulation and propagation of genome (chromosome) instability (Yurovet al., 2010, 2019; Andriani et al., 2017; Zhang and Vijg, 2018; Iourov et al., 2021). Since genome(chromosome) instability may result from viral infections (Heng, 2019), SARS-CoV-2 interactionswith cells of the central nervous system are able to increase the risk for early manifestationsof aging-related brain disorders and/or premature brain deterioration mediated by genome andchromosome instability. Recently, a number of studies dedicated to host-coronavirus proteininteraction networks have highlighted numerous molecular and cellular processes, which are likelyto be altered by SARS-CoV-2 (Gordon et al., 2020a; Lee et al., 2021; Schmidt et al., 2021; Terraccianoet al., 2021). Here, we have addressed data on SARS-CoV-2–host protein–protein interactomesfor assessing potential COVID-19 effects on aging-related genome (chromosome) instability inthe brain.Data on SARS-CoV-2–host protein–protein interactomes or networks were taken fromfollowing articles: Díaz (2020), Gordon et al. (2020a,b), Guzzi et al. (2020), Perrin-Cocon et al.(2020), Schmidt et al. (2021), and Terracciano et al. (2021). Candidate pathways (networks) weregrouped according to the association with processes involved in genome stability maintenance, cellcycle regulation, chromatin regulation, DNAmetabolism, and cell death. These clusters of pathwaysare generally associated with brain-specific chromosome/genome instability.Looking through the SARS-CoV-2–host interactomes, one may find a wide spectrum ofdifferent pathways affected by the coronavirus. For more details, see Díaz (2020), Gordonet al. (2020b), and Terracciano et al. (2021). However, each article reported on a small butsignificant proportion of pathways implicated in genome stability maintenance, DNA regulation,and chromatin organization. Taking into account previous evaluations of processes involved inbrain-specific chromosome/genome instability (Jeppesen et al., 2011; Yurov et al., 2011; Bajicet al., 2015; Caneus et al., 2018; Martínez-Cué and Rueda, 2020; Heng et al., 2021), followingcandidate pathways (pathway clusters) were selected: cell cycle, cell death, centrosome, chromatinorganization, DNA damage response, DNA regulation, DNA replication, DNA repair, ER stress,Iourov and Vorsanova COVID-19 and Genome (Chromosome) Instabilityand nucleotide metabolism. The rates of chromosome andgenome instability may increase with age being highlydependent on environmental factors (Iourov et al., 2020;Vorsanova et al., 2020). A viral infection may be such a factor(Heng et al., 2021). Therefore, according to interactomicdata, SARS-CoV-2 interactions with proteins involved inthe aforementioned pathways are able to initiate/stimulategenome and chromosome instability in neuronal cells.Figure 1 schematically depicts possible effects of SARS-CoV-2infection on the brain in the context of aging-related genome(chromosome) instability.Brain-specific genomic variations [including aneuploidy(loss/gain of whole chromosomes) and single gene mutations]are associated with a wide spectrum of late-onset braindiseases (Yurov et al., 2010; Rohrback et al., 2018; Iourovet al., 2021). More importantly, chromosome instabilityFIGURE 1 | Schematic representation of the possible effect of SARS-CoV-2infection (COVID-19) on the brain in the context of aging-related genome(chromosome) instability. Interactome analysis of SARS-CoV-2 infection hashighlighted a number of pathways to be potentially altered by the virus whichare listed at the bottom of the figure.mediates neurodegeneration (Iourov et al., 2009; Rohrbacket al., 2018; Yurov et al., 2019). Several molecular pathwayshave been associated with chromosome instability in theneurodegenerating brain including neuronal cell cycle errors,chromosome missegregation, and cellular senescence (Bajicet al., 2015; Caneus et al., 2018; Martínez-Cué and Rueda,2020). These processes are intimately linked to aging atmolecular, cellular, and tissular levels. For instance, prematureaging is associated with increased rates of chromosomeand genome instability. Natural aging is associated withaccumulation and propagation of somatic genome variations(e.g., aneuploidy) and genome instability. Alterations to genomestability maintenance may cause aging-related brain diseases orearly manifestations of late-onset neurodegenerative diseases(Yurov et al., 2010; Andriani et al., 2017; Zhang and Vijg,2018; Iourov et al., 2021). Additionally, DNA regulation andchromatin organization are able to affect genome stability byaltering the expression of genes implicated in the pathwaysdemonstrated in Figure 1. Since SARS-CoV-2 interactionswith proteins involved in genome stability maintenancepathways are able to contribute to chromosome/genomeinstability propagation, the coronavirus infection hasthe potential to cause neurobehavioral abnormalities,neurodegeneration (e.g., Alzheimer’s disease) and prematurebrain deterioration.SARS-CoV-2 infection possesses an appreciable effect onthe organism (Tu et al., 2020; Wu et al., 2020; Hu et al.,2021). Alterations to the central nervous system are observedin individuals with COVID-19 (Pennisi et al., 2020). Here, weexpress our opinion that SARS-CoV-2 may increase the riskfor neurobehavioral alterations and neurodegeneration mediatedby aging-related genome (chromosome) instability. Thus, SARS-CoV-2 is a potential risk factor for premature brain deterioration,Alzheimer’s disease and other late-onset neurodegenerativediseases. The opinion is supported by addressing SARS-CoV-2-host interactomes. It is to note that chromosome instabilitymediating complex diseases and aging is not specific for braindiseases (Yurov et al., 2010; Iourov et al., 2019, 2020; Vorsanovaet al., 2020). In other words, similar processes may occur in anytissue of an individual with SARS-CoV-2 infection. Additionally,other viruses are able to produce chromosome instability(Heng, 2019). Thus, one should be aware of the complicationscaused by chromosome and genome instability (e.g., canceror tissue degeneration) in individuals affected by COVID-19 infection. Moreover, these studies seem to be especiallyimportant for those who went through a cytokine storm, sincethe lattermay trigger tissue degeneration. Accordingly, molecularcytogenetic monitoring of chromosome and genome instability iswarranted in individuals with SARS-CoV-2 infection to preventgenome instability-mediated and aging-dependent pathologieson time.AUTHOR CONTRIBUTIONSII wrote the manuscript. Both authors conceived the idea andmade theoretical contributions.Frontiers in Aging Neuroscience | www.frontiersin.org 2 March 2022 | Volume 14 | Article 786264Iourov and Vorsanova COVID-19 and Genome (Chromosome) InstabilityFUNDINGAuthors were partially supported by RFBR and CITMAaccording to the Research Project No. 18-515-34005. Thework was partially supported by the Government Assignmentof the Russian Ministry of Science and Higher Education,Assignment No. AAAA-A19–119040490101-6 (Mental HealthResearch Center) and by the Government Assignment of theRussian Ministry of Health, Assignment No. 121031000238-1(Veltischev Research and Clinical Institute for Pediatrics).ACKNOWLEDGMENTSOur communication was dedicated to Yuri Yurov and IliaSoloviev. We express our sincere gratitude to Vasilisa Iurovafor Figure 1.REFERENCESAndriani, G. A., Vijg, J., and Montagna, C. (2017). Mechanisms and consequencesof aneuploidy and chromosome instability in the aging brain.Mech. Ageing Dev.161, 19–36. doi: 10.1016/j.mad.2016.03.007Bajic, V., Spremo-Potparevic, B., Zivkovic, L., Isenovic, E. R., and Arendt,T. (2015). Cohesion and the aneuploid phenotype in Alzheimer’s disease:a tale of genome instability. Neurosci. Biobehav. Rev. 55, 365–374.doi: 10.1016/j.neubiorev.2015.05.010Caneus, J., Granic, A., Rademakers, R., Dickson, D. 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The use,distribution or reproduction in other forums is permitted, provided the originalauthor(s) and the copyright owner(s) are credited and that the original publicationin this journal is cited, in accordance with accepted academic practice. No use,distribution or reproduction is permitted which does not comply with these terms.Frontiers in Aging Neuroscience | www.frontiersin.org 3 March 2022 | Volume 14 | Article 786264

COVID-19 and aging-related genome (chromosome) instability in the brain: another possible time-bomb of SARS-CoV-2 infection

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COVID-19 and aging-related genome (chromosome) instability in the brain: another possible time-bomb of SARS-CoV-2 infection

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