Cellular Senescence as a Mediator of Age-Related COVID-19 Severity

Wherever we find the intersection of inflammation and aging, important in many age-related conditions, it has become the case that attention is drawn to the role of senescent cells. Senescent cells cease replication, grow in size, and secrete a potent mix of inflammatory signals. Usually they self-destruct or are destroyed by the immune system shortly after entering a senescent state. Cells become senescent constantly throughout life, and for a variety of reasons, but only with advancing age do these cells linger and build up in number. Senescent cells serve a number of useful purposes when present in the short term, assisting in cancer suppression and wound healing, for example. When senescent cell signaling continues unabated, however, it disrupts tissue structure and function, and rouses the immune system to a state of chronic inflammation. This is an important contributing cause of degenerative aging.

SARS-CoV-2 is a novel betacoronavirus which infects the lower respiratory tract and can cause coronavirus disease 2019 (COVID-19), a complex respiratory distress syndrome. Epidemiological data show that COVID-19 has a rising mortality particularly in individuals with advanced age. Identifying a functional association between SARS-CoV-2 infection and the process of biological aging may provide a tractable avenue for therapy to prevent acute and long-term disease.

Here, we discuss how cellular senescence - a state of stable growth arrest characterized by pro-inflammatory and pro-disease functions - can hypothetically be a contributor to COVID-19 pathogenesis, and a potential pharmaceutical target to alleviate disease severity. First, we define why older COVID-19 patients are more likely to accumulate high levels of cellular senescence. Second, we describe how senescent cells can contribute to an uncontrolled SARS-CoV-2-mediated cytokine storm and an excessive inflammatory reaction during the early phase of the disease. Third, we discuss the various mechanisms by which senescent cells promote tissue damage leading to lung failure and multi-tissue dysfunctions. Fourth, we argue that a high senescence burst might negatively impact on vaccine efficacy.

Measuring the burst of cellular senescence could hypothetically serve as a predictor of COVID-19 severity, and targeting senescence-associated mechanisms prior and after SARS-CoV-2 infection might have the potential to limit a number of severe damages and to improve the efficacy of vaccinations.

Link: https://doi.org/10.1111/acel.13237



M.D. is co-founder, shareholder, and advisor of Cleara Biotech.

J.N. and M.D. wrote the manuscript with input from M.B., S.M., and T.G.B. M.D. supervised and planned the writing of the manuscript.

Posted by: Jones at September 30th, 2020 1:16 PM


September 24, 2020
Howard Hughes Medical Institute
Two new studies offer an explanation for why COVID-19 cases can be so variable. A subset of patients has mutations in key immunity genes; other patients have auto-antibodies that target the same components of the immune system. Both circumstances could contribute to severe forms of the disease.

Posted by: Jones at September 30th, 2020 1:18 PM


The ancient Neanderthal hand in severe COVID-19
September 30, 2020
Okinawa Institute of Science and Technology (OIST) Graduate University
Genetic variants that leave their carrier more susceptible to severe COVID-19 are inherited from Neanderthals, a new study finds.

"Obviously, factors such as your age and other diseases you may have also affect how severely you are affected by the virus. But among genetic factors, this is the strongest one."

Posted by: Jones at September 30th, 2020 1:40 PM

I've done three treatments of D&Q over the last 19 months and also have taken weekly rapamycin for 3 1/2 years. I contacted COVID-19 in early August and had minor symptoms and complete recovery in 3 days. 59M

Posted by: Larry at September 30th, 2020 3:28 PM

@Larry, and your age?

Posted by: Robert at September 30th, 2020 5:39 PM
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