TY - JOUR
T1 - COVID-19 and cellular senescence
AU - Schmitt, Clemens A.
AU - Tchkonia, Tamar
AU - Niedernhofer, Laura J.
AU - Robbins, Paul D.
AU - Kirkland, James L.
AU - Lee, Soyoung
N1 - Funding Information:
The authors apologize to all colleagues whose valuable insights and contributions to the discussed topic may have been missed or not explicitly mentioned owing to space restrictions. The authors thank numerous funding sources that enabled research at the intersection of senescence and COVID-19 in their laboratories, members of their research teams as well as their collaboration partners for helpful scientific exchange of conceptual ideas, controversies in the field, and clinical implications, as well as all the patients and their families, whose participation in clinical investigations and trials enhance our knowledge of pathogenetic mechanisms and therapeutic interventions.
Publisher Copyright:
© 2022, Springer Nature Limited.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
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U2 - 10.1038/s41577-022-00785-2
DO - 10.1038/s41577-022-00785-2
M3 - Article
C2 - 36198912
AN - SCOPUS:85139446838
SN - 1474-1733
VL - 23
SP - 251
EP - 263
JO - Nature Reviews Immunology
JF - Nature Reviews Immunology
IS - 4
ER -