The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is known to be more common in the elderly, who show also more severe symptoms and a higher risk of hospitalization and death. Here we show that the expression of the Angiotensin Converting Enzyme 2 (ACE2), the SARS-CoV2 cell receptor, increases during aging in mouse and human lungs, and following telomere shortening or dysfunction in mammalian cells and in mouse models. This increase is regulated at the transcription level, and Ace2 promoter activity is DNA damage response (DDR)-dependent. Indeed, ATM inhibition or the selective inhibition of telomeric DDR, through the use of antisense oligonucleotides, prevents Ace2 upregulation following telomere damage, in cultured cells and in mice. We propose that during aging telomeric shortening, by triggering DDR activation, causes the upregulation of ACE2, the SARS-CoV2 cell receptor, thus making the elderly likely more susceptible to the infection.

DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging / S. Sepe, F. Rossiello, V. Cancila, F. Iannelli, V. Matti, G. Cicio, M. Cabrini, E. Marinelli, B. Alabi, A. DI LILLO, A. Di Napoli, J. Shay, C. Tripodo, A. Fabrizio d'Adda di Fagagna. - (2021 Jun 09).

DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging

F. Rossiello;F. Iannelli;A. DI LILLO;
2021

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is known to be more common in the elderly, who show also more severe symptoms and a higher risk of hospitalization and death. Here we show that the expression of the Angiotensin Converting Enzyme 2 (ACE2), the SARS-CoV2 cell receptor, increases during aging in mouse and human lungs, and following telomere shortening or dysfunction in mammalian cells and in mouse models. This increase is regulated at the transcription level, and Ace2 promoter activity is DNA damage response (DDR)-dependent. Indeed, ATM inhibition or the selective inhibition of telomeric DDR, through the use of antisense oligonucleotides, prevents Ace2 upregulation following telomere damage, in cultured cells and in mice. We propose that during aging telomeric shortening, by triggering DDR activation, causes the upregulation of ACE2, the SARS-CoV2 cell receptor, thus making the elderly likely more susceptible to the infection.
Settore BIO/11 - Biologia Molecolare
https://www.biorxiv.org/content/10.1101/2021.06.09.447484v1
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/884689
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