226 results match your criteria ageing ace2


S19W, T27W, and N330Y mutations in ACE2 enhance SARS-CoV-2 S-RBD binding toward both wild-type and antibody-resistant viruses and its molecular basis.

Signal Transduct Target Ther 2021 Sep 16;6(1):343. Epub 2021 Sep 16.

West China Hospital Emergency Department (WCHED), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

SARS-CoV-2 recognizes, via its spike receptor-binding domain (S-RBD), human angiotensin-converting enzyme 2 (ACE2) to initiate infection. Ecto-domain protein of ACE2 can therefore function as a decoy. Here we show that mutations of S19W, T27W, and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding. Read More

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September 2021

Activation of angiotensin-converting enzyme 2/angiotensin (1-7)/mas receptor axis triggers autophagy and suppresses microglia proinflammatory polarization via forkhead box class O1 signaling.

Aging Cell 2021 Sep 16:e13480. Epub 2021 Sep 16.

Institute of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, China.

Brain renin-angiotensin (Ang) system (RAS) is implicated in neuroinflammation, a major characteristic of aging process. Angiotensin (Ang) II, produced by angiotensin-converting enzyme (ACE), activates immune system via angiotensin type 1 receptor (AT1), whereas Ang(1-7), generated by ACE2, binds with Mas receptor (MasR) to restrain excessive inflammatory response. Therefore, the present study aims to explore the relationship between RAS and neuroinflammation. Read More

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September 2021

Antihypertensive drug treatment and susceptibility to SARS-CoV-2 infection in human PSC-derived cardiomyocytes and primary endothelial cells.

Stem Cell Reports 2021 Sep 1. Epub 2021 Sep 1.

Department of Cellular and Molecular Medicine and Sarver Heart Center Molecular Cardiovascular Research Program, The University of Arizona, Tucson, AZ, USA; Department of Physiology, The University of Arizona, Tucson, AZ, USA; BIO5 Institute, The University of Arizona, Tucson, AZ, USA. Electronic address:

The pathogenicity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been attributed to its ability to enter through the membrane-bound angiotensin-converting enzyme 2 (ACE2) receptor. Therefore, it has been heavily speculated that angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy may modulate SARS-CoV-2 infection. In this study, exposure of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and human endothelial cells (hECs) to SARS-CoV-2 identified significant differences in protein coding genes involved in immunity, viral response, and cardiomyocyte/endothelial structure. Read More

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September 2021

ACE2 Netlas: Functional Characterization and Drug-Gene Interactions of Gene Network to Understand Its Potential Involvement in COVID-19 Susceptibility.

Front Genet 2021 27;12:698033. Epub 2021 Aug 27.

Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States.

Angiotensin-converting enzyme-2 () receptor has been identified as the key adhesion molecule for the transmission of the SARS-CoV-2. However, there is no evidence that human genetic variation in ACE2 is singularly responsible for COVID-19 susceptibility. Therefore, we performed an integrative multi-level characterization of genes that interact with ACE2 (ACE2-gene network) for their statistically enriched biological properties in the context of COVID-19. Read More

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Deamidation drives molecular aging of the SARS-CoV-2 spike protein receptor-binding motif.

J Biol Chem 2021 Sep 6:101175. Epub 2021 Sep 6.

Instituto de Nanobiotecnologıa (NANOBIOTEC), UBA-CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina. Electronic address:

The spike protein is the main protein component of the SARS-CoV-2 virion surface. The spike receptor-binding motif mediates recognition of the human angiotensin-converting enzyme 2 (hACE2) receptor, a critical step in infection, and is the preferential target for spike-neutralizing antibodies. Post-translational modifications of the spike receptor-binding motif have been shown to modulate viral infectivity and host immune response, but these modifications are still being explored. Read More

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September 2021

Annelid genomes: Enchytraeus crypticus, a soil model for the innate (and primed) immune system.

Lab Anim (NY) 2021 Sep 6. Epub 2021 Sep 6.

Department of Biosciences, Aarhus University, Silkeborg, Denmark.

Enchytraeids (Annelida) are soil invertebrates with worldwide distribution that have served as ecotoxicology models for over 20 years. We present the first high-quality reference genome of Enchytraeus crypticus, assembled from a combination of Pacific Bioscience single-molecule real-time and Illumina sequencing platforms as a 525.2 Mbp genome (910 gapless scaffolds and 18,452 genes). Read More

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September 2021

Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2.

Signal Transduct Target Ther 2021 09 1;6(1):328. Epub 2021 Sep 1.

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- and interleukin 6 (IL-6)-secreting cells and C-X-C motif chemokine receptor 3 (CXCR3)+ cells in lung tissue of old RMs. Read More

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September 2021

Angiotensin-Converting Enzyme 2 (ACE2) in the Context of Respiratory Diseases and Its Importance in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

Pharmaceuticals (Basel) 2021 Aug 17;14(8). Epub 2021 Aug 17.

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico.

Angiotensin-Converting Enzyme 2 (ACE2) is an 805 amino acid protein encoded by the ACE2 gene expressed in various human cells, especially in those located in the epithelia. The primary function of ACE2 is to produce angiotensin (1-7) from angiotensin II (Ang II). The current research has described the importance of ACE2 and Ang (1-7) in alternative routes of the renin-angiotensin system (RAS) that promote the downregulation of fibrosis, inflammation, and oxidative stress processes in a great variety of diseases, such as hypertension, acute lung injury, liver cirrhosis, and kidney abnormalities. Read More

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The potential role of abnormal angiotensin-converting enzyme 2 expression correlated with immune infiltration after SARS-CoV-2 infection in the prognosis of breast cancer.

Aging (Albany NY) 2021 Aug 19;13(undefined). Epub 2021 Aug 19.

Department of Cardiology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, P.R. China.

The potential role of abnormal ACE2 expression after SARS-CoV-2 infection in the prognosis of breast cancer is still ambiguous. In this study, we analyzed ACE2 changes in breast cancer and studied the correlation between ACE2 and the prognosis and further analyzed the relationship between immune infiltration and the prognosis of different breast cancer subtypes. Finally, we inferred the prognosis of breast cancer patients after SARS-CoV-2 infection. Read More

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Gut microbiota and renin-angiotensin system: a complex interplay at local and systemic levels.

Am J Physiol Gastrointest Liver Physiol 2021 08 18. Epub 2021 Aug 18.

Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.

Gut microbiota is a potent biological modulator of many physiological and pathological states. The renin-angiotensin system (RAS), including the local gastrointestinal RAS (GI RAS), emerges as a potential mediator of microbiota-related effects. The RAS is involved in cardiovascular system homeostasis, water-electrolyte balance, intestinal absorption, glycemic control, inflammation, carcinogenesis and aging-related processes. Read More

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A Machine-Generated View of the Role of Blood Glucose Levels in the Severity of COVID-19.

Front Public Health 2021 28;9:695139. Epub 2021 Jul 28.

Blue Brain Project, École polytechnique fédérale de Lausanne (EPFL), Geneva, Switzerland.

SARS-CoV-2 started spreading toward the end of 2019 causing COVID-19, a disease that reached pandemic proportions among the human population within months. The reasons for the spectrum of differences in the severity of the disease across the population, and in particular why the disease affects more severely the aging population and those with specific preconditions are unclear. We developed machine learning models to mine 240,000 scientific articles openly accessible in the CORD-19 database, and constructed knowledge graphs to synthesize the extracted information and navigate the collective knowledge in an attempt to search for a potential common underlying reason for disease severity. Read More

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Expression of SARS-CoV-2 Entry Factors in Human Alveolar Type II Cells in Aging and Emphysema.

Biomedicines 2021 Jul 6;9(7). Epub 2021 Jul 6.

Department of Thoracic Medicine and Surgery, Temple University, Philadelphia, PA 19140, USA.

Alveolar type II (ATII) cells proliferate and restore the injured epithelium. It has been described that SARS-CoV-2 infection causes diffuse alveolar damage in the lungs. However, host factors facilitating virus infection in ATII cells are not well known. Read More

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Aging & COVID-19 susceptibility, disease severity, and clinical outcomes: The role of entangled risk factors.

Exp Gerontol 2021 Aug 3;154:111507. Epub 2021 Aug 3.

Padova Neuroscience Center (PNC), Department of Neuroscience, University of Padova, Padova, Italy. Electronic address:

The emergence of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) in late 2019 has been associated with a high rate of mortality and morbidity. It has been determined that the old population are not only at an increased risk for affliction with COVID-19 infection, but also atypical presentations, severe forms of the disease, and mortality are more common in this population. A plethora of mechanisms and risk factors contribute to the higher risk of infection in the old population. Read More

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An ACE2/Mas-related receptor MrgE axis in dopaminergic neuron mitochondria.

Redox Biol 2021 Jul 22;46:102078. Epub 2021 Jul 22.

Cellular and Molecular Neurobiology of Parkinson's Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, Santiago de Compostela; Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain. Electronic address:

ACE2 plays a pivotal role in the balance between the pro-oxidative pro-inflammatory and the anti-oxidative anti-inflammatory arms of the renin-angiotensin system. Furthermore, ACE2 is the entry receptor for SARS-CoV-2. Clarification of ACE2-related mechanisms is crucial for the understanding of COVID-19 and other oxidative stress and inflammation-related processes. Read More

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SARS-CoV-2: is there neuroinvasion?

Fluids Barriers CNS 2021 Jul 14;18(1):32. Epub 2021 Jul 14.

Department of Neuroscience, University of Rochester, URMC, 601 Elmwood Avenue, Rochester, NY, 14642, USA.

Background: SARS-CoV-2, a coronavirus (CoV), is known to cause acute respiratory distress syndrome, and a number of non-respiratory complications, particularly in older male patients with prior health conditions, such as obesity, diabetes and hypertension. These prior health conditions are associated with vascular dysfunction, and the CoV disease 2019 (COVID-19) complications include multiorgan failure and neurological problems. While the main route of entry into the body is inhalation, this virus has been found in many tissues, including the choroid plexus and meningeal vessels, and in neurons and CSF. Read More

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A bivalent recombinant vaccine targeting the S1 protein induces neutralizing antibodies against both SARS-CoV-2 variants and wild-type of the virus.

MedComm (Beijing) 2021 May 17. Epub 2021 May 17.

Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics West China Hospital, Sichuan University Chengdu China.

The emerging variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in pandemic call for the urgent development of universal corona virus disease 2019 (COVID-19) vaccines which could be effective for both wild-type SARS-CoV-2 and mutant strains. In the current study, we formulated protein subunit vaccines with AS03 adjuvant and recombinant proteins of S1 subunit of SARS-CoV-2 (S1-WT) and S1 variant (K417N, E484K, N501Y, and D614G) subunit (S1-Mut), and immunized transgenic mice that express human angiotensin-converting enzyme 2 (hACE2). The S1 protein-specific antibody production and the neutralization capability for SARS-CoV-2 and B. Read More

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The urgent need for more basic research on SARS-Cov2 infection and vaccines in assessing potential psychoneurological effects using maternal immune activation (MIA) and other preclinical modeling.

Authors:
William J Murphy

Brain Behav Immun 2021 Jul 1. Epub 2021 Jul 1.

Departments of Dermatology and Internal Medicine, UC Davis School of Medicine, Sacramento, CA, United States. Electronic address:

The rapid development and application of different SARS-Cov2 vaccines world-wide has resulted in impressive efficacy and protection from this deadly pandemic. However, the existence of different and continuously developing vaccine candidates coupled with the likelihood of continued application due to both waning immune responses and emergence of viral mutants, means that more basic research regarding their efficacy and continued application are needed. This is particularly true with use of preclinical models involving effects when given during pregnancy. Read More

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Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors.

Int J Mol Sci 2021 Jun 7;22(11). Epub 2021 Jun 7.

Laboratory of Epigenetics, Istituti Clinici Scientifici Maugeri IRCCS, Via Maugeri 10, 27100 Pavia, Italy.

The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Read More

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A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry.

Nat Commun 2021 06 23;12(1):3907. Epub 2021 Jun 23.

Aging Institute, University of Pittsburgh/UPMC, Pittsburgh, PA, USA.

SARS-CoV-2 (2019-nCoV) is the pathogenic coronavirus responsible for the global pandemic of COVID-19 disease. The Spike (S) protein of SARS-CoV-2 attaches to host lung epithelial cells through the cell surface receptor ACE2, a process dependent on host proteases including TMPRSS2. Here, we identify small molecules that reduce surface expression of TMPRSS2 using a library of 2,560 FDA-approved or current clinical trial compounds. Read More

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Ageing, ACE2 deficiency and bad outcome in COVID-19.

Clin Chem Lab Med 2021 06 14;59(10):1607-1609. Epub 2021 Jun 14.

Fondazione Umbra Cuore e Ipertensione-ONLUS and Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy.

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The key role of the level of ACE2 gene expression in SARS-CoV-2 infection.

Aging (Albany NY) 2021 Jun 11;13(11):14552-14556. Epub 2021 Jun 11.

Department of Clinical Research and Innovation, Foch Hospital, Suresnes, France.

SARS-CoV-2 more readily affects the elderly, especially as they present co-morbidities. In the COVID-19 pathogeny, ACE2 appears to be the key cell receptor for SARS-CoV-2 to infect humans. The level of ACE2 gene expression influences the susceptibility of contracting SARS-CoV-2. Read More

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Human Type II Taste Cells Express Angiotensin-Converting Enzyme 2 and Are Infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

Am J Pathol 2021 09 6;191(9):1511-1519. Epub 2021 Jun 6.

National Institute on Aging/Intramural Program, Baltimore Maryland. Electronic address:

Chemosensory changes are well-reported symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The virus targets cells for entry by binding of its spike protein to cell-surface angiotensin-converting enzyme 2 (ACE2). It is not known whether ACE2 is expressed on taste receptor cells (TRCs), or whether TRCs are infected directly. Read More

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September 2021

Cellular Tropism of SARS-CoV-2 across Human Tissues and Age-related Expression of ACE2 and TMPRSS2 in Immune-inflammatory Stromal Cells.

Authors:
Ming Zheng

Aging Dis 2021 Jun 1;12(3):718-725. Epub 2021 Jun 1.

1Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing, China.

Recently, emerging evidence has indicated that COVID-19 represents a major threat to older populations, but the underlying mechanisms remain unclear. The pathogen causing COVID-19 is acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection depends on the key entry factors, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Read More

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Construction of a Human Cell Landscape of COVID-19 Infection at Single-cell Level.

Aging Dis 2021 Jun 1;12(3):705-709. Epub 2021 Jun 1.

1State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

COVID-19 is now causing a global pandemic, there is a demand to explain the different clinical patterns between children and adults. To clarify the organs/cell types vulnerable to COVID-19 infection and the potential age-depended expression patterns of five factors (, , , , ) associated with clinical symptoms. In this study, we analyzed expression levels of five COVID-19 host dependency factors in multiple adult and fetal human organs. Read More

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Ischemic Stroke: An Underestimated Complication of COVID-19.

Aging Dis 2021 Jun 1;12(3):691-704. Epub 2021 Jun 1.

1Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

The coronavirus disease 2019 (COVID-19) has spread rapidly as a pandemic around the world. In addition to severe acute respiratory syndrome, more and more studies have focused on the complication of COVID-19, especially ischemic stroke. Here, we propose several pathophysiological processes and possible mechanisms underlying ischemic stroke after COVID-19 for early prevention and better treatment of COVID-19-related stroke. Read More

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Do inflammaging and coagul-aging play a role as conditions contributing to the co-occurrence of the severe hyper-inflammatory state and deadly coagulopathy during COVID-19 in older people?

Exp Gerontol 2021 08 26;151:111423. Epub 2021 May 26.

Department of Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, PR China. Electronic address:

The coronavirus disease 2019 (COVID-19) is a new infectious respiratory disease, which has caused a pandemic that has become the world's leading public health emergency, threatening people of all ages worldwide, especially the elderly. Complications of COVID-19 are closely related to an upregulation of the inflammatory response revealed by the pro-inflammatory profile of plasma cytokines (to the point of causing a cytokine storm), which is also a contributing cause of the associated coagulation disorders with venous and arterial thromboembolisms, causing multiple organ dysfunction and failure. In severe fulminant cases of COVID-19, there is an activation of coagulation and consumption of clotting factors leading to a deadly disseminated intravascular coagulation (DIC). Read More

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Extremes of age are associated with differences in the expression of selected pattern recognition receptor genes and ACE2, the receptor for SARS-CoV-2: implications for the epidemiology of COVID-19 disease.

BMC Med Genomics 2021 05 24;14(1):138. Epub 2021 May 24.

Department of Surgery, University of California San Diego, La Jolla, CA, USA.

Background: Older aged adults and those with pre-existing conditions are at highest risk for severe COVID-19 associated outcomes.

Methods: Using a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts (GSE113957) we investigated whether age affects the expression of pattern recognition receptor (PRR) genes and ACE2, the receptor for SARS-CoV-2.

Results: Extremes of age are associated with increased expression of selected PRR genes, ACE2 and four genes that encode proteins that have been shown to interact with SAR2-CoV-2 proteins. Read More

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Endocrine and metabolic aspects of COVID-19.

Endokrynol Pol 2021 19;72(3):256-260. Epub 2021 May 19.

Department of Neuroendocrinology, Medical University of Lodz, Lodz, Poland.

The paper presents the theoretical considerations on the role of endocrine and metabolic alterations accompanying COVID-19 infection. These alterations may be presumed on the basis of the following two observations. Firstly, the virus SARS-CoV-2 responsible for the COVID-19 infection uses an important renin-angiotensin system (RAS) element - angiotensin-converting enzyme 2 (ACE2) - as a receptor protein for entry into target cells and, in consequence, disturbs the function of the main (circulating) renin-angiotensin-aldosterone system (RAAS) and of the local renin-angiotensin system localized in different tissues and organs. Read More

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ZMPSTE24 Regulates SARS-CoV-2 Spike Protein-enhanced Expression of Endothelial PAI-1.

Am J Respir Cell Mol Biol 2021 09;65(3):300-308

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland; and.

Endothelial dysfunction is implicated in the thrombotic events reported in patients with coronavirus disease (COVID-19), but the underlying molecular mechanisms are unknown. Circulating levels of the coagulation cascade activator PAI-1 are substantially higher in patients with COVID-19 with severe respiratory dysfunction than in patients with bacterial sepsis and acute respiratory distress syndrome. Indeed, the elevation of PAI-1 is recognized as an early marker of endothelial dysfunction. Read More

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September 2021

Implications of Low-grade Inflammation in SARS-CoV-2 Immunopathology.

MEDICC Rev 2021 Apr 30;23(2):42. Epub 2021 Apr 30.

Immunology Laboratory, National Oncology and Radiobiology Institute (INOR), Havana, Cuba.

Introduction: Advanced age and chronic disease comorbidities are indicators of poor prognosis in COVID-19 clinical progression. Fatal outcomes in patients with these characteristics are due to a dysfunctional immune response. Understanding COVID-19's immunopathogenesis helps in designing strategies to prevent and mitigate complications during treatment. Read More

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