PT  - JOURNAL ARTICLE
AU  - Sara Sepe
AU  - Francesca Rossiello
AU  - Valeria Cancila
AU  - Fabio Iannelli
AU  - Valentina Matti
AU  - Giada Cicio
AU  - Matteo Cabrini
AU  - Eugenia Marinelli
AU  - Busola Alabi
AU  - Alessia di Lillo
AU  - Arianna Di Napoli
AU  - Jerry W. Shay
AU  - Claudio Tripodo
AU  - Fabrizio d’Adda di Fagagna
TI  - DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging
AID  - 10.1101/2021.06.09.447484
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.09.447484
4099  - http://biorxiv.org/content/early/2021/06/09/2021.06.09.447484.short
4100  - http://biorxiv.org/content/early/2021/06/09/2021.06.09.447484.full
AB  - 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.Competing Interest StatementF.R. and F.dA.d.F. are inventors on the patent applications PCT/EP2013/059753 and PCT/EP2016/068162