Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease

Lynch, Seodhna M.; Guo, Guangran; Gibson, David; Bjourson, Anthony J.; Singh, Taranjit

doi:10.3390/cells10123367

Cited by 59 publications

(41 citation statements)

References 274 publications

(319 reference statements)

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“…In this regard, placental fusogen syncyctin-2 induces immunosuppression necessary for maternal acceptance of the allogeneic fetus, while syncytin-1 triggers placental senescence and immune activation to initiate labor ( Cox and Redman, 2017 ; Gal et al., 2019 ; Lokossou et al., 2020 ; Roberts et al., 2021 ). Viral hijacking of these particular fusogens augments infection by disabling host immune defenses and establishing a virus-friendly environment marked by elevated cytosolic calcium, abundant intracellular iron, and low interferon type I ( Martin and Bernard, 2018 ; Frisch and MacFawn, 2020 ; Lynch et al., 2021 ). As cell-cell fusion is a major trigger of cellular senescence, viruses may have developed the ability to exploit host fusogens, promoting premature aging ( Gal et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Osorio

Sfera

Anton

et al. 2022

Front. Cell. Infect. Microbiol.

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A growing body of epidemiological and research data has associated neurotropic viruses with accelerated brain aging and increased risk of neurodegenerative disorders. Many viruses replicate optimally in senescent cells, as they offer a hospitable microenvironment with persistently elevated cytosolic calcium, abundant intracellular iron, and low interferon type I. As cell-cell fusion is a major driver of cellular senescence, many viruses have developed the ability to promote this phenotype by forming syncytia. Cell-cell fusion is associated with immunosuppression mediated by phosphatidylserine externalization that enable viruses to evade host defenses. In hosts, virus-induced immune dysfunction and premature cellular senescence may predispose to neurodegenerative disorders. This concept is supported by novel studies that found postinfectious cognitive dysfunction in several viral illnesses, including human immunodeficiency virus-1, herpes simplex virus-1, and SARS-CoV-2. Virus-induced pathological syncytia may provide a unified framework for conceptualizing neuronal cell cycle reentry, aneuploidy, somatic mosaicism, viral spreading of pathological Tau and elimination of viable synapses and neurons by neurotoxic astrocytes and microglia. In this narrative review, we take a closer look at cell-cell fusion and vesicular merger in the pathogenesis of neurodegenerative disorders. We present a “decentralized” information processing model that conceptualizes neurodegeneration as a systemic illness, triggered by cytoskeletal pathology. We also discuss strategies for reversing cell-cell fusion, including, TMEM16F inhibitors, calcium channel blockers, senolytics, and tubulin stabilizing agents. Finally, going beyond neurodegeneration, we examine the potential benefit of harnessing fusion as a therapeutic strategy in regenerative medicine.

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Section: Introductionmentioning

confidence: 99%

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Osorio

Sfera

Anton

et al. 2022

Front. Cell. Infect. Microbiol.

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“…In rodent models, senescent T cells can induce diabetes and obesity, while their clearance moderates the disease [13,14]. It is therefore tempting to speculate that one reason for the susceptibility of the aged, and those with chronic diseases such as rheumatoid arthritis and diabetes, is due to the higher prevalence of senescent cells in these patients, including those of the immune system [15]. Similarly, T cell immunosenescence is closely related to the development of cardiovascular disease [16], another chronic disease state associated with susceptibility to severe COVID-19 disease [17].…”

Section: Host Susceptibility To Sars-cov-2 21 Ageing and Covid-19mentioning

confidence: 99%

The AI-Assisted Identification and Clinical Efficacy of Baricitinib in the Treatment of COVID-19

et al. 2022

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During the current pandemic, the vast majority of COVID-19 patients experienced mild symptoms, but some had a potentially fatal aberrant hyperinflammatory immune reaction characterized by high levels of IL-6 and other cytokines. Modulation of this immune reaction has proven to be the only method of reducing mortality in severe and critical COVID-19. The anti-inflammatory drug baricitinib (Olumiant) has recently been strongly recommended by the WHO for use in COVID-19 patients because it reduces the risk of progressive disease and death. It is a Janus Kinase (JAK) 1/2 inhibitor approved for rheumatoid arthritis which was suggested in early 2020 as a treatment for COVID-19. In this review the AI-assisted identification of baricitinib, its antiviral and anti-inflammatory properties, and efficacy in clinical trials are discussed and compared with those of other immune modulators including glucocorticoids, IL-6 and IL-1 receptor blockers and other JAK inhibitors. Baricitinib inhibits both virus infection and cytokine signalling and is not only important for COVID-19 management but is “non-immunological”, and so should remain effective if new SARS-CoV-2 variants escape immune control. The repurposing of baricitinib is an example of how advanced artificial intelligence (AI) can quickly identify new drug candidates that have clinical benefit in previously unsuspected therapeutic areas.

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“…Increasing age, male sex and deterioration in cognitive and physical activity have been demonstrated to be independent predictors of mortality in COVID-19 patients [64]. Therefore, the importance of timely diagnosis and individualized restorative management for elderly patients is emphasized [65]. Positive potential effects of systemic steroids on the management of COVID-19 have been demonstrated [66].…”

Section: Age-related Strategies For Long Covid-19 Rehabilitationmentioning

confidence: 99%

The Role of Physical Medicine and Rehabilitation in Long Covid-19 Management

Koçyiğit¹

2022

AAEE

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COVID-19 is an infectious disease that can have a multi-system involvement, most notably, the respiratory tract. After acute infection, a considerable proportion of patients suffer from persistent symptoms and signs, defined as long COVID-19. Depending on the affected systems and organs, patients can experience various clinic pictures. Rehabilitation approaches serve a crucial role in providing functional recovery and improving quality of life for COVID-19 survivors. As a result of the wideness of the clinical spectrum of the long COVID-19, rehabilitation practices differ according to the affected systems. Therefore, the formation of multidisciplinary rehabilitation teams is an inevitable necessity. The establishment of specific centers for long COVID-19 rehabilitation will be beneficial. If it is not possible, existing rehabilitation centers should be strengthened for this purpose. Since the pulmonary system and respiratory tract are the most affected structures, one of the main issues to be considered in long COVID-19 cases is cardiopulmonary rehabilitation. Patients experience musculoskeletal disorders such as atrophy, sarcopenia, poor physical performance and contracture due to long-term hospitalization, intensive care treatment, quarantine practices and immobilization. Rehabilitation practices also focus on these disorders. All rehabilitation practices in long COVID-19 patients should start with low intensity, and parameters such as intensity and frequency should be increased as the patient's tolerance improves. In high-risk cases, parameters including oxygen saturation, blood pressure, and heart rhythm should be monitored. Health-care authorities should prioritize the rehabilitation of the long COVID-19 syndrome and invest in this area. Authorities, physicians and patients should collaborate to facilitate long COVID-19 rehabilitation and to establish a self-contained system.

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Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease

Cited by 59 publications

References 274 publications

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

The AI-Assisted Identification and Clinical Efficacy of Baricitinib in the Treatment of COVID-19

The Role of Physical Medicine and Rehabilitation in Long Covid-19 Management

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