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Nature: The new coronavirus (COVID-19) will accelerate cell aging, but it also provides a new direction for treatment.
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Nature: The new coronavirus (COVID-19) will accelerate cell aging, but it also provides a new direction for treatment.
Since the outbreak of the COVID-19 epidemic, human understanding of the virus has been constantly refreshed. As a “flying disaster” for the entire human race, its scope and scope of influence have become larger and larger, and it has profoundly affected the social order of mankind.
Not only that, the new coronavirus (SARS-CoV-2), as a deadly virus, is also extremely harmful to infected patients.
On June 23, 2021, a study in the medical journal Nature Medicine showed that more than half of patients with mild neo-COVID-19 disease had various symptoms after six months of recovery, such as dyspnea, loss of taste and smell, fatigue, and decreased memory [1].
It is worth noting that after a cell is infected by a virus, it usually activates its own aging mechanism and rapidly decays. This is considered to be a way for the body to resist virus infection.
So, does SARS-CoV-2 infection also cause cell senescence? If so, how can we use this mechanism to fight the COVID-19 pandemic?
On September 13, 2021, researchers from the Charité Medical School in Berlin, Germany, published a research paper titled: Virus-induced senescence is driver and therapeutic target in COVID-19 in Nature [2].
This study shows that after the host cell is infected with the new coronavirus (SARS-CoV-2), it will wake up its own cellular senescence mechanism as the main stress response.
Based on this, the researchers used Senolytics therapy for senescent cells to selectively eliminate cells infected with the new coronavirus, thus revealing a new virus treatment plan.
Virus infection can significantly cause cell damage and cause profound biological changes in the infected host cell, such as turning on the virus-triggered cell senescence switch. Virus-induced senescence (VIS) is no different from other forms of cellular senescence, and is accompanied by a senescence-related secretory phenotype (SASP).
Aging-related secretions are mainly composed of pro-inflammatory cytokines, extracellular matrix active factors, and procoagulant factors. They are also the basis for cytokine storm, macrophage activation, NET formation, endotheliitis, and widespread pulmonary thrombosis. The derailment of cytokines and immune cell networks is the cause of the organ damage and clinical severity of COVID-19.
From this point of view, virus-induced senescence (VIS) plays an important role in the development of COVID-19 symptoms, and studying the relationship between the two may become the key to the treatment of patients with COVID-19 infection.
In this study, the researchers found that the airway mucosa in situ aging markers and serum SASP factor levels in patients with COVID-19 were elevated. At the same time, in vitro tests showed that COVID-19 patients exhibited macrophage activation, SASP-related secretion, complement lysis, and SASP amplifies secondary senescence of endothelial cells.
This confirms that SARS-CoV-2, like other viruses, can also awaken cell senescence as the main stress response of infected cells.
COVID-19 patients exhibit virus-induced aging (VIS) characteristics
So, how can virus-induced senescence (VIS) be applied to the treatment of COVID-19 patients?
In 2015, a research team led by Dr. James Kirkland of the Mayo Clinic in the United States published a research paper on Aging Cell titled: The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs [3], reporting a type of selective killing The drug combination of senescent cells-Senolytics.
Senolytics is composed of dasatinib and quercetin, which can selectively induce the death of senescent cells. Among them, dasatinib can eliminate aging human adipocyte progenitor cells, while quercetin can kill aging human endothelial cells and mouse bone marrow stem cells. The combination of the two has a stronger effect.
Based on this, the research team tried to link the host cell senescence caused by SARS-CoV-2 with Senolytics in order to develop a new targeted treatment strategy for COVID-19.
The researchers constructed SARS-CoV-2 infected hamster and mouse models, and verified their conjecture by injecting Navitoclax and Dasatinib/quercetin and other Senolytics treatment combinations. They found that Senolytics can selectively eliminate virus-induced senescent cells, alleviate lung diseases associated with COVID-19, and reduce inflammation.
Senolytics therapy can alleviate the disease characteristics of COVID-19 in animal models and patients
The author stated: “The results of this study show that virus-induced senescence (VIS) is a key trigger for COVID-19-related cytokine upgrade and organ damage. Therefore, we suggest that the hemolytic targeting of virus-infected cells is a new Treatment plan to combat SARS-CoV-2 or other viral infections.”
VIS cells are sensitive to the targeting effect of Senolytics
All in all, this study reveals that SARS-CoV-2 infection can also cause stress-induced senescence of host cells. Therefore, Senolytics therapy targeting senescent cells can be used to eliminate SARS-CoV-2 infected cells to develop a A new targeted treatment method for COVID-19.
In fact, this is not the first study linking Senolytics with COVID-19. On July 16, 2021, a research team from the University of Minnesota and the Mayo Medical Center published a titled Senolytics reduce coronavirus-related mortality in the Science Journal. in old mice’s research paper [4].
This study shows that the anti-aging drug Senolytics can reduce the death rate associated with the coronavirus in elderly mice.
references:
1. https://www.nature.com/articles/s41591-021-01433-3
2. https://www.nature.com/articles/s41586-021-03995-1
3. https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12344
4. https://science.sciencemag.org//373/6552/eabe4832
(source:internet, reference only)
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