tetano
Editor, Senior Moderator
Nat Rev Immunol
. 2022 Oct 5.
doi: 10.1038/s41577-022-00785-2. Online ahead of print.
COVID-19 and cellular senescence
Clemens A Schmitt[SUP] 1 2 3 4 5 [/SUP], Tamar Tchkonia[SUP] 6 [/SUP], Laura J Niedernhofer[SUP] 7 [/SUP], Paul D Robbins[SUP] 7 [/SUP], James L Kirkland[SUP] 6 [/SUP], Soyoung Lee[SUP] 8 9 10 [/SUP]
Affiliations
Abstract
The clinical severity of coronavirus disease 2019 (COVID-19) is largely determined by host factors. Recent advances point to cellular senescence, an ageing-related switch in cellular state, as a critical regulator of SARS-CoV-2-evoked hyperinflammation. SARS-CoV-2, like other viruses, can induce senescence and exacerbates the senescence-associated secretory phenotype (SASP), which is comprised largely of pro-inflammatory, extracellular matrix-degrading, complement-activating and pro-coagulatory factors secreted by senescent cells. These effects are enhanced in elderly individuals who have an increased proportion of pre-existing senescent cells in their tissues. SASP factors can contribute to a 'cytokine storm', tissue-destructive immune cell infiltration, endothelialitis (endotheliitis), fibrosis and microthrombosis. SASP-driven spreading of cellular senescence uncouples tissue injury from direct SARS-CoV-2-inflicted cellular damage in a paracrine fashion and can further amplify the SASP by increasing the burden of senescent cells. Preclinical and early clinical studies indicate that targeted elimination of senescent cells may offer a novel therapeutic opportunity to attenuate clinical deterioration in COVID-19 and improve resilience following infection with SARS-CoV-2 or other pathogens.
. 2022 Oct 5.
doi: 10.1038/s41577-022-00785-2. Online ahead of print.
COVID-19 and cellular senescence
Clemens A Schmitt[SUP] 1 2 3 4 5 [/SUP], Tamar Tchkonia[SUP] 6 [/SUP], Laura J Niedernhofer[SUP] 7 [/SUP], Paul D Robbins[SUP] 7 [/SUP], James L Kirkland[SUP] 6 [/SUP], Soyoung Lee[SUP] 8 9 10 [/SUP]
Affiliations
- PMID: 36198912
- DOI: 10.1038/s41577-022-00785-2
Abstract
The clinical severity of coronavirus disease 2019 (COVID-19) is largely determined by host factors. Recent advances point to cellular senescence, an ageing-related switch in cellular state, as a critical regulator of SARS-CoV-2-evoked hyperinflammation. SARS-CoV-2, like other viruses, can induce senescence and exacerbates the senescence-associated secretory phenotype (SASP), which is comprised largely of pro-inflammatory, extracellular matrix-degrading, complement-activating and pro-coagulatory factors secreted by senescent cells. These effects are enhanced in elderly individuals who have an increased proportion of pre-existing senescent cells in their tissues. SASP factors can contribute to a 'cytokine storm', tissue-destructive immune cell infiltration, endothelialitis (endotheliitis), fibrosis and microthrombosis. SASP-driven spreading of cellular senescence uncouples tissue injury from direct SARS-CoV-2-inflicted cellular damage in a paracrine fashion and can further amplify the SASP by increasing the burden of senescent cells. Preclinical and early clinical studies indicate that targeted elimination of senescent cells may offer a novel therapeutic opportunity to attenuate clinical deterioration in COVID-19 and improve resilience following infection with SARS-CoV-2 or other pathogens.