DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging.
EMBO Rep
; 23(2): e53658, 2022 02 03.
Article
in English
| MEDLINE | ID: covidwho-1547826
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), known to be more common in the elderly, who also show more severe symptoms and are at higher risk of hospitalization and death. Here, we show that the expression of the angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, increases during aging in mouse and human lungs. ACE2 expression increases upon telomere shortening or dysfunction in both cultured mammalian cells and in vivo in mice. This increase is controlled at the transcriptional level, and Ace2 promoter activity is DNA damage response (DDR)-dependent. Both pharmacological global DDR inhibition of ATM kinase activity and selective telomeric DDR inhibition by the use of antisense oligonucleotides prevent Ace2 upregulation following telomere damage in cultured cells and in mice. We propose that during aging telomere dysfunction due to telomeric shortening or damage triggers DDR activation and this causes the upregulation of ACE2, the SARS-CoV-2 cell receptor, thus contributing to make the elderly more susceptible to the infection.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
DNA Damage
/
Aging
/
Telomere
/
Angiotensin-Converting Enzyme 2
/
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Aged
/
Animals
/
Humans
Language:
English
Journal:
EMBO Rep
Journal subject:
Molecular Biology
Year:
2022
Document Type:
Article
Affiliation country:
Embr.202153658
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