Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats

Malavolta, Marco; Giacconi, Robertina; Brunetti, Dario; Provinciali, Mauro; Maggi, Fabrizio

doi:10.3390/cells9040909

Cited by 67 publications

(57 citation statements)

References 100 publications

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“…Identifying the role of senescence in infections may provide the rational to design therapeutic interventions based on senolytics to eliminate senescent cells as a mean to manage persistent infections or overwhelming host immunoresponses as recently suggested for HIV and SARS-CoV-2 [118][119][120].…”

Section: Discussionmentioning

confidence: 99%

Senescence and Host–Pathogen Interactions

Humphreys

ElGhazaly

Frisan

2020

Cells

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Damage to our genomes triggers cellular senescence characterised by stable cell cycle arrest and a pro-inflammatory secretome that prevents the unrestricted growth of cells with pathological potential. In this way, senescence can be considered a powerful innate defence against cancer and viral infection. However, damage accumulated during ageing increases the number of senescent cells and this contributes to the chronic inflammation and deregulation of the immune function, which increases susceptibility to infectious disease in ageing organisms. Bacterial and viral pathogens are masters of exploiting weak points to establish infection and cause devastating diseases. This review considers the emerging importance of senescence in the host–pathogen interaction: we discuss the pathogen exploitation of ageing cells and senescence as a novel hijack target of bacterial pathogens that deploys senescence-inducing toxins to promote infection. The persistent induction of senescence by pathogens, mediated directly through virulence determinants or indirectly through inflammation and chronic infection, also contributes to age-related pathologies such as cancer. This review highlights the dichotomous role of senescence in infection: an innate defence that is exploited by pathogens to cause disease.

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Section: Discussionmentioning

confidence: 99%

Senescence and Host–Pathogen Interactions

Humphreys

ElGhazaly

Frisan

2020

Cells

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“…For instance, vesicular stomatitis virus replication is markedly impaired in both primary and tumor senescent cells in comparison with non-senescent cells [51]. Other examples of viral induced cellular senescence include dengue, Epstein-Barr, HIV-1, measles, as well as the virulence factor, NSI protein, of the influenza A virus [52]. While it is still unclear whether SARS-CoV-2 induces cellular senescence, this possibility should be explored in the future in older COVID-19 survivors.…”

Section: Covid-19 and Mechanisms Of Inflammaging In Older Individualsmentioning

confidence: 99%

A public health perspective of aging: do hyper-inflammatory syndromes such as COVID-19, SARS, ARDS, cytokine storm syndrome, and post-ICU syndrome accelerate short- and long-term inflammaging?

et al. 2020

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A central clinical question as the world deals with the COVID-19 pandemic is what the long-term sequelae for the millions of individuals will be who recover from the hyperinflammatory state characterizing COVID-19 and in particular for the hundreds of thousands who are ill enough to need hospitalization and in particular ICU care. Even when the pandemic is finally controlled, will COVID-19 survivors face exaggerated internal inflammatory processes, worsening co-morbidities, and increased susceptibility to age-related diseases? Clues for what may happen in post-COVID-19 patients can be elicited from those who recovered from other conditions that lead to similar hyperinflammatory states such as Severe Acute Respiratory Syndrome (SARS), acute respiratory disease syndrome (ARDS), cytokine storm syndrome, and post-ICU syndrome. The short-and long-term sequalae following recovery from each of these conditions suggests that these syndromes lead to an accelerated state of chronic subclinical systemic inflammation often seen in aging (termed inflammaging) resulting in increased and worsening age-related conditions including frailty even in younger individuals.

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“…Thus, an increased presence of senescent cells may predispose to the development of severe COVID-19 via two mechanisms: ( 1 ) reduced immune cell clearance by contributing to the aforementioned inflammation-induced suppression of innate and adaptive immunity ( 204 , 205 , 225 ) and ( 3 ) increasing viral load by acting as a site of enhanced SARS-CoV-2 replication. Interestingly, a number of clinical trials assessing the therapeutic benefit of drugs that directly eliminate senescent cells or suppress their SASP are already underway in patients with COVID-19 ( 223 , 226 ). Results of such studies will help researchers address whether a high senescent cell burden is indeed a risk factor for the development of severe COVID-19.…”

Section: Pathogen Eliminationmentioning

confidence: 99%

Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19?

Hazeldine

Lord

2020

Front. Immunol.

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Bearing a strong resemblance to the phenotypic and functional remodeling of the immune system that occurs during aging (termed immunesenescence), the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), is characterized by an expansion of inflammatory monocytes, functional exhaustion of lymphocytes, dysregulated myeloid responses and the presence of highly activated senescent T cells. Alongside advanced age, male gender and pre-existing co-morbidities [e.g., obesity and type 2 diabetes (T2D)] are emerging as significant risk factors for COVID-19. Interestingly, immunesenescence is more profound in males when compared to females, whilst accelerated aging of the immune system, termed premature immunesenescence, has been described in obese subjects and T2D patients. Thus, as three distinct demographic groups with an increased susceptibility to COVID-19 share a common immune profile, could immunesenescence be a generic contributory factor in the development of severe COVID-19? Here, by focussing on three key aspects of an immune response, namely pathogen recognition, elimination and resolution, we address this question by discussing how immunesenescence may weaken or exacerbate the immune response to SARS-CoV-2. We also highlight how aspects of immunesenescence could render potential COVID-19 treatments less effective in older adults and draw attention to certain therapeutic options, which by reversing or circumventing certain features of immunesenescence may prove to be beneficial for the treatment of groups at high risk of severe COVID-19.

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Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats

Cited by 67 publications

References 100 publications

Senescence and Host–Pathogen Interactions

Senescence and Host–Pathogen Interactions

A public health perspective of aging: do hyper-inflammatory syndromes such as COVID-19, SARS, ARDS, cytokine storm syndrome, and post-ICU syndrome accelerate short- and long-term inflammaging?

Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19?

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