scholarly journals Intersection between ageing-related Genes and SARS-CoV-2 Interactome: Is it higher than expected?

Author(s):  
Pietro Hiram Guzzi ◽  
Elisabetta Pedace ◽  
Federico Manuel Giorgi

Abstract Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease, 2019; COVID-19) is associated with adverse outcomes in patients. It has been observed that lethality seems to be related to the age of patients. Moreover, it has been demonstrated that ageing causes some modifications at a molecular level.Objective: The study aims to investigate a possible link between the increased COVID-19 lethality and the molecular changes that occur in elderly people.Methods: We considered publicly available datasets on ageing-related genes and SARS-CoV-2 interactors. Then, for each SARS-CoV-2 protein interactor, we tested for the enrichment of ageing-related proteins. Finally, we performed a network-based analysis to identify which molecular mechanisms could play a role in the SARS-CoV-2 molecular aetiology and ultimately affect COVID-19 outcome.Results: We observed a significant intersection between some SARS-CoV-2 interactors and ageing-related genes. Our analysis evidenced that virus infection particularly affects ageing molecular mechanisms centred around proteins EEF2, NPM1, HMGA1, HMGA2, APEX1, CHEK1, PRKDC, and GPX4.Conclusion: Our study generated a mechanistic framework aiming at explaining the correlation between COVID-19 incidence in elderly patients and molecular mechanisms of ageing. This will provide testable hypotheses for future investigation on the mechanism of action of coronaviruses and pharmacological solutions tailored on specific age ranges.

2020 ◽  
Author(s):  
Pietro Hiram Guzzi ◽  
Elisabetta Pedace ◽  
Federico Manuel Giorgi

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease, 2019; COVID-19) is associated with adverse outcomes in patients. It has been observed that lethality seems to be related to the age of patients. Moreover, it has been demonstrated that ageing causes some modifications at a molecular level.Objective The study aims to investigate a possible link between the increased COVID-19 lethality and the molecular changes that occur in elderly people.Methods We considered publicly available datasets on ageing-related genes and SARS-CoV-2 interactors. Then, for each SARS-CoV-2 protein interactor, we tested for the enrichment of ageing-related proteins. Finally, we performed a network-based analysis to identify which molecular mechanisms could play a role in the SARS-CoV-2 molecular aetiology and ultimately affect COVID-19 outcome.Results We observed a significant intersection between some SARS-CoV-2 interactors and ageing-related genes. Our analysis evidenced that virus infection particularly affects ageing molecular mechanisms centred around proteins EEF2, NPM1, HMGA1, HMGA2, APEX1, CHEK1, PRKDC, and GPX4.Conclusion Our study generated a mechanistic framework aiming at explaining the correlation between COVID-19 incidence in elderly patients and molecular mechanisms of ageing. This will provide testable hypotheses for future investigation on the mechanism of action of coronaviruses and pharmacological solutions tailored on specific age ranges.


2017 ◽  
Vol 72 (5-6) ◽  
pp. 181-196
Author(s):  
Cheng Libao ◽  
Jiang Runzhi ◽  
Yang Mengli ◽  
Li Liangjun ◽  
Li Shuyan

AbstractAdventitious roots (ARs) directly affect lotus seedling growth and product quality because principal root is not well developed. However, the details of AR formation at the molecular level have not been determined in lotus. Therefore, three stages were chosen to identify the change of proteins abundant during rhizome formation, using isobaric tags for relative and absolute quantization coupled with liquid chromatography–tandem mass spectrometry to gain insight into the molecular mechanisms involved in AR formation. We totally obtained 323,375 spectra during AR formation. After filtering to eliminate low-scoring spectra, 66,943 spectra, including 53,106 unique spectra, were identified. These unique spectra matched 28,905 peptides, including 24,992 unique peptides, which were assembled into 6686 proteins. In the C0/C1 and C1/C2 stages, 66 and 32 proteins showed enhanced abundance, and 173 and 73 proteins showed decreased abundance, respectively. Seventeen important AR formation-related proteins from the three stages were identified, and the expressions of nine genes from the above-identified proteins were assessed by qRT-PCR. This article provides a comprehensive understanding of the changes in metabolism during AR formation, and is helpful to accelerate the progress of breeding in fulture in lotus root.


2021 ◽  
Author(s):  
Daniele Mercatelli ◽  
Elisabetta Pedace ◽  
Federico Manuel Giorgi ◽  
Pietro Hiram Guzzi

Motivation: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease, 2019; COVID-19) is associated with adverse outcomes in patients. It has been observed that lethality seems to be related to the age of patients. Moreover, it has been demonstrated that ageing causes some modifications at a molecular level. Objective: The study aims to shed out light on a possible link between the increased COVID-19 lethality and the molecular changes that occur in elderly people. Methods: We considered public datasets on ageing-related genes and their expression at tissue level. We selected interactors that are known to be related to ageing process. Then, we performed a networkbased analysis to identify interactors significantly related to both SARS-CoV-2 and ageing. Finally, we investigated changes on the expression level of coding genes at tissue, gender and age level. Results We observed a significant intersection between some SARS-CoV-2 interactors and ageing-related genes suggesting that those genes are particularly affected by COVID-19 infection. Our analysis evidenced that virus infection particularly affects ageing molecular mechanisms centred around proteins EEF2, NPM1, HMGA1, HMGA2, APEX1, CHEK1, PRKDC, and GPX4. We found that HMGA1, and NPM1 have a different expression in lung of males, while HMGA1, APEX1, CHEK1, EEF2, and NPM1 present changes in expression in males due to aging effects. Conclusion Our study generated a mechanistic framework to explaining the correlation between COVID-19 incidence in elderly patients and molecular mechanisms of ageing. This will provide testable hypotheses for future investigation and pharmacological solutions tailored on specific age ranges.


2020 ◽  
Vol 13 (1) ◽  
pp. 658-666
Author(s):  
Tossapon Chamnankit ◽  
Parichat Ong-artborirak ◽  
Jukkrit Wangrath

Background: Elderly people with uncontrolled diabetes mellitus (DM) are at risk of falls, which can lead to injury and disability. Not much is known of informal caregivers’ awareness of falls in elderly patients with DM. Objective: This study aims to identify an association between caregiver’s awareness and falls in elderly patients with DM. Methods: A total of 136 pairs of DM patients and their respective family caregivers were recruited from a clinical service center at Chiang Mai University, Thailand. The questionnaire regarding the caregiver’s awareness of the risk of falls in elderly patients was given via a face-to-face interview. Each elderly patient was asked about their history of falls in the prior year, and the risk of falls was assessed by Time Up & Go (TUG) test. Logistic regression analysis was performed to determine association. Results: The mean age of the DM patients was 65.7 years. Sixty-two patients (45.6%) had fallen at least once in the prior year. The mean TUG test result was 12.67±1.83 second. Most caregivers demonstrated a high level of awareness regarding the risk of falls in elderly patients. The results of the multivariable analysis showed that three variables – balance problems, risk of falls assessed by TUG test, and scores of caregiver’s awareness of risk of falls – were significantly related to falls in the previous year among elderly patients with DM (p-value<0.05). Conclusion: The caregivers’ awareness of fall risk may influence fall occurrence among older adults with DM. An intervention program to improve awareness among informal caregivers should be considered for fall prevention in elderly people.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Na Jiang ◽  
Xiaoyu Zhang ◽  
Xuejun Gu ◽  
Xiaozhuang Li ◽  
Lei Shang

AbstractLong non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides but not translated into proteins. LncRNAs regulate gene expressions at multiple levels, such as chromatin, transcription, and post-transcription. Further, lncRNAs participate in various biological processes such as cell differentiation, cell cycle regulation, and maintenance of stem cell pluripotency. We have previously reported that lncRNAs are closely related to programmed cell death (PCD), which includes apoptosis, autophagy, necroptosis, and ferroptosis. Overexpression of lncRNA can suppress the extrinsic apoptosis pathway by downregulating of membrane receptors and protect tumor cells by inhibiting the expression of necroptosis-related proteins. Some lncRNAs can also act as competitive endogenous RNA to prevent oxidation, thereby inhibiting ferroptosis, while some are known to activate autophagy. The relationship between lncRNA and PCD has promising implications in clinical research, and reports have highlighted this relationship in various cancers such as non-small cell lung cancer and gastric cancer. This review systematically summarizes the advances in the understanding of the molecular mechanisms through which lncRNAs impact PCD.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1754
Author(s):  
Giuseppe Garroni ◽  
Francesca Balzano ◽  
Sara Cruciani ◽  
Renzo Pala ◽  
Donatella Coradduzza ◽  
...  

Human adipose tissue-derived stem cells (hADSCs) are highly suitable for regeneration therapies being easily collected and propagated in vitro. The effects of different external factors and culturing conditions are able to affect hADSC proliferation, senescence, differentiation, and migration, even at the molecular level. In the present paper, we exposed hADSCs to an exhausted medium from the breast cancer cell line (MCF-7) to evaluate whether the soluble factors released by these cells may be able to induce changes in stem cell behavior. In particular, we investigated the expression of stemness-related genes (OCT4; Sox 2; Nanog), the cell-cycle regulators p21 (WAF1/CIP1) p53, epigenetic markers (DNMT1 and Sirt1), and autophagy-related proteins. From our results, we can infer that the exhausted medium from MCF-7 is able to influence the hADSCs behavior increasing the expression of stemness-related genes, cell proliferation, and autophagy. Polyamines detectable in MCF-7 exhausted medium could be related to the higher proliferation capability observed in hADSCs, suggesting direct crosstalk between these molecules and the observed changes in stem cell potency.


Author(s):  
Sam Schoenmakers ◽  
Pauline Snijder ◽  
Robert M Verdijk ◽  
Thijs Kuiken ◽  
Sylvia S M Kamphuis ◽  
...  

Abstract Background In general, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy is not considered to be an increased risk for severe maternal outcomes but has been associated with an increased risk for fetal distress. Maternal-fetal transmission of SARS-CoV-2 was initially deemed uncertain; however, recently a few cases of vertical transmission have been reported. The intrauterine mechanisms, besides direct vertical transmission, leading to the perinatal adverse outcomes are not well understood. Methods Multiple maternal, placental, and neonatal swabs were collected for the detection of SARS-CoV-2 using real-time quantitative polymerase chain reaction (RT-qPCR). Serology of immunoglobulins against SARS-CoV-2 was tested in maternal, umbilical cord, and neonatal blood. Placental examination included immunohistochemical investigation against SARS-CoV-2 antigen expression, with SARS-CoV-2 ribonucleic acid (RNA) in situ hybridization and transmission electron microscopy. Results RT-qPCRs of the oropharynx, maternal blood, vagina, placenta, and urine were all positive over a period of 6 days, while breast milk, feces, and all neonatal samples tested negative. Placental findings showed the presence of SARS-CoV-2 particles with generalized inflammation characterized by histiocytic intervillositis with diffuse perivillous fibrin depositions with damage to the syncytiotrophoblasts. Conclusions Placental infection by SARS-CoV-2 leads to fibrin depositions hampering fetal-maternal gas exchange with resulting fetal distress necessitating a premature emergency cesarean section. Postpartum, the neonate showed a fetal or pediatric inflammatory multisystem-like syndrome with coronary artery ectasia temporarily associated with SARS-CoV-2 for which admittance and care on the neonatal intensive care unit (NICU) were required, despite being negative for SARS-CoV-2. This highlights the need for awareness of adverse fetal and neonatal outcomes during the current coronavirus disease 2019 pandemic, especially considering that the majority of pregnant women appear asymptomatic.


2021 ◽  
Vol 7 (2) ◽  
pp. 30
Author(s):  
Laeya Baldini ◽  
Bruno Charpentier ◽  
Stéphane Labialle

Box C/D small nucleolar RNAs (C/D snoRNAs) represent an ancient family of small non-coding RNAs that are classically viewed as housekeeping guides for the 2′-O-methylation of ribosomal RNA in Archaea and Eukaryotes. However, an extensive set of studies now argues that they are involved in mechanisms that go well beyond this function. Here, we present these pieces of evidence in light of the current comprehension of the molecular mechanisms that control C/D snoRNA expression and function. From this inventory emerges that an accurate description of these activities at a molecular level is required to let the snoRNA field enter in a second age of maturity.


2021 ◽  
Vol 6 (2) ◽  
pp. 48
Author(s):  
Elisa Innocenzi ◽  
Ida Cariati ◽  
Emanuela De Domenico ◽  
Erika Tiberi ◽  
Giovanna D’Arcangelo ◽  
...  

Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and NRXN3) have been identified, each encoding for α and β neurexins, from two independent promoters. Moreover, each Nrxns gene (1–3) has several alternative exons and produces many splice variants that bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength, and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We showed that exercise promoted Nrxns1–3 AS at splice site 4 (SS4) both in α and β isoforms, inducing a switch from exon-excluded isoforms (SS4−) to exon-included isoforms (SS4+) in FC but not in hippocampus. Additionally, we showed that the same AE program enhanced the expression level of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show molecular changes.


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